The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.

BACKGROUND: Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. MAIN BODY: In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. CONCLUSION: Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

In silico development of a novel anti-mutation, multi-epitope mRNA vaccine against MPXV variants of emerging lineage and sub-lineages by using immunoinformatics approaches.

Over the past year, an unexpected surge in human monkeypox (hMPX) cases has been observed. This outbreak differs from previous ones, displaying distinct epidemiological characteristics and transmission patterns, believed to be influenced by a newly emerging monkeypox virus (MPXV) lineage. Notably, this emerging MPXV lineage has exhibited several non-synonymous mutations, some of which are linked to immunomodulatory activities and antigenic characteristics that aid in host detection. However, specific treatments or vaccines for human monkeypox are currently lacking. Hence, we aim to develop a multi-epitope mRNA vaccine by using immunoinformatics approaches against the MPXV, particularly its emerging variants. Six proteins (A29L, A35R, B6R, M1R, H3L, and E8L) were chosen for epitope and mutation site identification. Seventeen top-performing epitopes and eight epitopes containing mutation sites were selected and combined with adjuvants, the PADRE sequence, and linkers for vaccine development. The molecular and physical properties of the designed vaccine (WLmpx) were favorable. Immunological characteristics of WLmpx were assessed through molecular docking, molecular dynamics (MD) simulations, and immune simulations. Finally, the vaccine sequence was utilized to formulate an mRNA-based vaccine. The informatics-based predicted results indicated that the designed vaccine exhibits significant potential in eliciting high-level humoral and cellular immune responses, but further validation through in vivo and vitro studies is warranted.Communicated by Ramaswamy H. Sarma.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

Novel Sm3+-doped La3Ga5MO14 (M = Si or Ge) phosphors for indoor illumination: effects of M cations on photoluminescence.

A series of La3(1-x)Ga5MO14:xSm3+ (M = Si or Ge) orange-red phosphors with high color purity, low correlated color temperature, and good thermal stability were successfully synthesized via a high-temperature solid-phase technique. The phase structure and morphology of La3Ga5SiO14(LGSi):xSm3+ and La3Ga5GeO14(LGGe):xSm3+ were investigated. Sm3+-doped LGSi and LGGe phosphors emitted orange-red light under an excitation of 403 nm, and the optimal doping concentrations were 3 mol% and 2 mol% with excellent color purities of 98.46% and 98.25%, respectively. The concentration quenching mechanism of both the samples was dominated by dipole-dipole interaction, and the effect of Si4+ and Ge4+ on luminescence performance was discussed. The internal quantum efficiencies of LGSi:0.03Sm3+ and LGGe:0.02Sm3+ were calculated to be 27.14% and 56.07%, respectively. The CIE and CCT values indicated that the luminescence of the prepared phosphors was in the orange-red region. Additionally, a white light-emitting diode (w-LED) was fabricated with LGGe:0.02Sm3+ phosphors, which was capable of emitting bright and warm white light and exhibiting a high color rendering index (CRI) of 87.17 and an appropriate correlated color temperature (CCT) of 6108 K. These results indicated that the prepared phosphors with excellent luminescent performances have potential application in indoor illumination.

Novel Operation Mechanism and Multifunctional Applications of Bubble Microrobots.

Microrobots have emerged as powerful tools for manipulating particles, cells, and assembling biological tissue structures at the microscale. However, achieving precise and flexible operation of arbitrary-shaped microstructures in 3D space remains a challenge. In this study, three novel operation methods based on bubble microrobots are proposed to enable delicate and multifunctional manipulation of various microstructures. These methods include 3D turnover, fixed-point rotation, and 3D ejection. By harnessing the combined principles of the effect of the heat flow field and surface tension of an optothermally generated bubble, the bubble microrobot can perform tasks such as flipping an SIA humanoid structure, rotating a bird-like structure, and launching a hollow rocket-like structure. The proposed multi-mode operation of bubble microrobots enables diverse attitude adjustments of microstructures with different sizes and shapes in both 2D and 3D spaces. As a demonstration, a biological microenvironment of brain glioblastoma is constructed by the bubble microrobot. The simplicity, versatility, and flexibility of this proposed method hold great promise for applications in micromanipulation, assembly, and tissue engineering.

Dual-Responsive Nanorobot-Based Marsupial Robotic System for Intracranial Cross-Scale Targeting Drug Delivery.

Nanorobots capable of active movement are an exciting technology for targeted therapeutic intervention. However, the extensive motion range and hindrance of the blood-brain barrier impeded their clinical translation in glioblastoma therapy. Here, a marsupial robotic system constructed by integrating chemical/magnetic hybrid nanorobots (child robots) with a miniature magnetic continuum robot (mother robot) for intracranial cross-scale targeting drug delivery is reported. For primary targeting on macroscale, the continuum robot enters the cranial cavity through a minimally invasive channel (e.g., Ommaya device) in the skull and transports the nanorobots to pathogenic regions. Upon circumventing the blood-brain barrier, the released nanorobots perform secondary targeting on microscale to further enhance the spatial resolution of drug delivery. In vitro experiments against primary glioblastoma cells derived from different patients are conducted for personalized treatment guidance. The operation feasibility within organisms is shown in ex vivo swine brain experiments. The biosafety of the treatment system is suggested in in vivo experiments. Owing to the hierarchical targeting method, the targeting rate, targeting accuracy, and treatment efficacy have improved greatly. The marsupial robotic system offers a novel intracranial local therapeutic strategy and constitutes a key milestone in the development of glioblastoma treatment platforms.

Efficient and Homogeneous Carbonitriding of High-Entropy Alloys by a Mechanochemical Process for Obtaining Coordinated Electromagnetic Matching.

Optimizing the impedance matching via electromagnetic adjustment is considered an effective strategy to accomplish exceptional electromagnetic wave absorption (EMA) performance. Here, we report an efficient and green process to obtain the carbonitriding FeCoNiCr high-entropy alloys (HEAs) with flake-shaped morphology by using organic cyanide (Dicyandiamide, C2H4N4) as nitrogen and carbon sources. The carbonitriding effects on the phase structure, magnetic properties, mechanical hardness, corrosion resistance, high-temperature oxidation resistance, and EMA performances were investigated systematically. The carbonitriding process optimized the impedance match by decreasing the dielectric constant via introducing the nonmetallic C and N. The #CN10 sample exhibited outstanding EMA performances with a minimum reflection loss of -32.3 dB at 7.89 GHz and a broad effective bandwidth of 4.46 GHz, which covered the majority of X-band. In addition, the carbonitriding FeCoNiCr HEAs had great mechanical properties, excellent corrosion resistance, and high-temperature oxidation resistance, indicating excellent adaptability to harsh environments as well as good EMA performances. This work provides a new idea for the preparation and design of carbonitriding EMA materials.

Tumor microenvironment remodeling plus immunotherapy could be used in mesenchymal-like tumor with high tumor residual and drug resistant rate.

Epithelial-mesenchymal transition (EMT) is a common process during tumor progression and is always related to residual tumor, drug resistance and immune suppression. However, considering the heterogeneity in EMT process, there is still a need to establish robust EMT classification system with reasonable molecular, biological and clinical implications to investigate whether these unfavorable survival factors are common or unique in different individuals. In our work, we classify tumors with four EMT status, that is, EMTlow, EMTmid, EMThigh-NOS (Not Otherwise Specified), and EMThigh-AKT (AKT pathway overactivation) subtypes. We find that EMThigh-NOS subtype is driven by intrinsic somatic alterations. While, EMThigh-AKT subtype is maintained by extrinsic cellular interplay between tumor cells and macrophages in an AKT-dependent manner. EMThigh-AKT subtype is both unresectable and drug resistant while EMThigh-NOS subtype can be treated with cell cycle related drugs. Importantly, AKT activation in EMThigh-AKT not only enhances EMT process, but also contributes to the immunosuppressive microenvironment. By remodeling tumor immune-microenvironment by AKT inhibition, EMThigh-AKT can be treated by immune checkpoint blockade therapies. Meanwhile, we develop TumorMT website ( http://tumormt.neuroscience.org.cn/ ) to apply this EMT classification and provide reasonable therapeutic guidance.

Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection.

Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.

Pyroelectric catalytic performance of Sm3+-modified Pb(Mg1/3Nb2/3)O3-PbTiO3 for organic dyes: degradation efficiency, kinetics and pyroelectric catalytic mechanism.

The development of photocatalysis is hindered, in part, by the quick recombination of photogenerated carriers and the instability of light sources. In this study, the problem of too-fast electron-hole pair compounding in photocatalysis is effectively regulated by the polarization field of pyroelectric materials using the pyroelectric method. Self-polarized pyroelectric materials that depend on temperature variations can generate usable electrical energy and polarized charge carriers to degrade organic pollutants. Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) is a relaxor ferroelectric material with spontaneous polarization characteristics. The PMN-0.30PT:1 mol%Sm3+ catalyst was prepared by applying the high-temperature solid-state reaction method. Under the dark condition and nine cold-hot cycles of 23 °C-68 °C, using H2O2-assisted PMN-0.30PT:1 mol%Sm3+ as a catalyst, the degradation rate of rhodamine 6G (10 mg L-1) was 94.3 ± 2.5%. In addition, the degradation rates of 88.52% and 64.32% were obtained for rhodamine B (10 mg L-1) and methylene blue (10 mg L-1), respectively. This study provides a new approach to the pyroelectric catalytic degradation of organic pollutants.

Multifunctional amorphous FeCoNiTixSi high-entropy alloys with excellent electromagnetic-wave absorption performances.

Amorphous high-entropy alloys (HEAs) as electromagnetic-wave absorbing materials have been rarely reported. In this work, amorphous FeCoNiTixSi HEAs were synthesized by introducing a high content of large-atom Ti using the high-energy ball-milling technique. This amorphous structure could improve the saturated magnetization and coercivity of HEAs, but slightly degraded the mechanical and oxidation resistance properties. In terms of electromagnetic properties, FeCoNiTi0.01Si and FeCoNiTiSi exhibit excellent electromagnetic-wave absorption performances, with significant absorptions of -68.4 dB at 6.14 GHz and -63.4 dB at 9.12 GHz, corresponding to bandwidths of 5.15 GHz (1.69 mm) and 3.64 GHz (1.43 mm), respectively. Overall, the prepared FeCoNiTixSi HEAs exhibited superior comprehensive performances compared to other HEA absorption materials. This work provided a novel strategy for the development of new electromagnetic-wave absorption materials with low weight, high absorption efficiency, and resistance to harsh environments.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).

A Deep Learning Model for Automatic Segmentation of Intraparenchymal and Intraventricular Hemorrhage for Catheter Puncture Path Planning.

Intracerebral hemorrhage is the subtype of stroke with the highest mortality rate, especially when it also causes secondary intraventricular hemorrhage. The optimal surgical option for intracerebral hemorrhage remains one of the most controversial areas of neurosurgery. We aim to develop a deep learning model for the automatic segmentation of intraparenchymal and intraventricular hemorrhage for clinical catheter puncture path planning. First, we develop a 3D U-Net embedded with a multi-scale boundary aware module and a consistency loss for segmenting two types of hematoma in computed tomography images. The multi-scale boundary aware module can improve the model's ability to understand the two types of hematoma boundaries. The consistency loss can reduce the probability of classifying a pixel into two categories at the same time. Since different hematoma volumes and locations have different treatments. We also measure hematoma volume, estimate centroid deviation, and compare with clinical methods. Finally, we plan the puncture path and conduct clinical validation. We collected a total of 351 cases, and the test set contained 103 cases. For intraparenchymal hematomas, the accuracy can reach 96 % when the proposed method is applied for path planning. For intraventricular hematomas, the proposed model's segmentation efficiency and centroid prediction are superior to other comparable models. Experimental results and clinical practice show that the proposed model has potential for clinical application. In addition, our proposed method has no complicated modules and improves efficiency, with generalization ability.

Relationships Between Perceived Organizational Support, Psychological Capital and Work Engagement Among Chinese Infection Control Nurses.

Background: Few studies have focused on the work engagement of infection control nurses (ICNs). The perceived organizational support (POS) and psychological capital (PsyCap) might be important factors influencing ICNs' work engagement. Moreover, PsyCap might play a mediating role in the relationship between POS and work engagement. Objective: This study aims to clarify the relationships among POS, PsyCap and work engagement of Chinese ICNs. Methods: A cross-sectional design was performed to collect data on 7382 ICNs from 20 provinces in China. Data collection was conducted by an online questionnaire, including questions about demographics, the Chinese version of the Utrecht work engagement scale (UWES), the Chinese version of the psychological capital questionnaire (PCQ) and the perceived organizational support scale for medical staff. Univariate analysis, the Spearman correlation method and the mediating effect test were conducted. Results: The work engagement was at a relatively high level, with a total score of 80.87 ± 14.95. The total scores of POS and PsyCap scale were 41.45 ± 7.37 and 89.14 ± 9.06 respectively, both of which were at the upper-middle level. Work engagement was positively associated with both POS and PsyCap (both P<0.01). Furthermore, the mediating effect of PsyCap on the relationship between POS and work engagement was 0.394, the total effect was 0.443, and the ratio of mediating effect to total effect was 88.94%. Conclusion: The findings suggest that both POS and PsyCap can directly increase the work engagement of the Chinese ICNs. Besides, POS can indirectly improve work engagement, partially through PsyCap. Therefore, enhancing POS and PsyCap could be effective in improving the work engagement of ICNs.

Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli.

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.

Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches.

Background: Since May 2022, cases of monkeypox, a zoonotic disease caused by the monkeypox virus (MPXV), have been increasingly reported worldwide. There are, however, no proven therapies or vaccines available for monkeypox. In this study, several multi-epitope vaccines were designed against the MPXV using immunoinformatics approaches. Methods: Three target proteins, A35R and B6R, enveloped virion (EV) form-derived antigens, and H3L, expressed on the mature virion (MV) form, were selected for epitope identification. The shortlisted epitopes were fused with appropriate adjuvants and linkers to vaccine candidates. The biophysical andbiochemical features of vaccine candidates were evaluated. The Molecular docking and molecular dynamics(MD) simulation were run to understand the binding mode and binding stability between the vaccines and Toll-like receptors (TLRs) and major histocompatibility complexes (MHCs). The immunogenicity of the designed vaccines was evaluated via immune simulation. Results: Five vaccine constructs (MPXV-1-5) were formed. After the evaluation of various immunological and physicochemical parameters, MPXV-2 and MPXV-5 were selected for further analysis. The results of molecular docking showed that the MPXV-2 and MPXV-5 had a stronger affinity to TLRs (TLR2 and TLR4) and MHC (HLA-A*02:01 and HLA-DRB1*02:01) molecules, and the analyses of molecular dynamics (MD) simulation have further confirmed the strong binding stability of MPXV-2 and MPXV-5 with TLRs and MHC molecules. The results of the immune simulation indicated that both MPXV-2 and MPXV-5 could effectively induce robust protective immune responses in the human body. Conclusion: The MPXV-2 and MPXV-5 have good efficacy against the MPXV in theory, but further studies are required to validate their safety and efficacy.

Primary Intracranial Ewing Sarcoma Invading the Superior Sagittal Sinus with EWSR1-FLI1 Gene Fusion and EWSR1 Gene Mutation: A Case Report and Literature Review.

BACKGROUND: Primary intracranial Ewing sarcoma (ES) is an extremely rare intracranial malignant tumor, mostly occurring in children and adolescents. Because of its rarity, the magnetic resonance imaging (MRI) features and treatment strategies of primary intracranial ES are still unclear. METHODS: The purpose of this study was therefore to report a case of primary intracranial ES, whose molecular features included both EWSR1-FLI1 (EWS RNA binding protein 1- Friend leukemia integration 1) gene fusion and EWSR1 gene mutation. It is worth noting that this is the first reported case of ES invading the superior sagittal sinus and mostly causing occlusion. At the same time, there were polymorphisms of four drug metabolism-related enzymes in the tumor. Subsequently, we conducted a literature review to characterize the clinical features, imaging findings, pathological features, treatments, and prognoses of primary intracranial ESs. RESULTS: A 21-year-old female was admitted to the hospital with headache with nausea and vomiting for 2 weeks. An MRI showed a 3.8 × 4.0 cm large heterogeneous mass in the bilateral parietal lobe with peritumoral edema. The tumor invaded the superior sagittal sinus and mostly caused occlusion of the middle segment of the superior sagittal sinus. The mass was successfully removed using a neuromicroscope. Postoperative pathology indicated a primary intracranial ES. High throughput sequencing (next generation sequencing) showed that there was EWSR1-FLI1 gene fusion and EWSR1 gene mutation in the tumor, with polymorphisms of four drug metabolism-related enzymes and low tumor mutational burden. Subsequently, the patient received intensity modulated radiation therapy. The patient has signed an informed consent form. CONCLUSIONS: The diagnosis of primary intracranial ES depended on histopathology, immunohistochemistry staining, and genetic testing. At present, total tumor resection combined with radiotherapy and chemotherapy is the most effective treatment. We report the first case of primary intracranial ES invading the superior sagittal sinus and causing middle segment occlusion, accompanied by EWSR1-FLI1 gene fusion and EWSR1 gene mutation.

Endoscopic transorbital approach for skull base lesions: a report of 16 clinical cases.

Due to the deep location, complex anatomy, and adjacent vital neurovascular structures, skull base surgery is challenging and requires specific approaches. The emerging endoscopic transorbital approach (eTOA) technique provides a new approach to the orbital content, spheno-orbital region, lateral cavernous sinus, and Meckel's cave. In this study, the clinical utility and effectiveness of the eTOA are reported. Sixteen cases who underwent the eTOA were included in the current study. The patients were divided into 3 groups according to tumor location: Group A (intraorbital, 6 cases), group B (spheno-orbital, 7 cases), and group C (cavernous sinus, and Meckel's cave, 3 cases). The clinical data and surgical results were analyzed. Eight meningiomas, 2 hemangiomas, 1 low-grade glioma, 1 instance of inflammatory hyperplasia tissue, 1 Langerhans cell histiocytosis, 1 epidermoid cyst, 1 trigeminal schwannoma, and 1 bone fibrosis hyperplasia were observed. The mean tumor diameter was 2.4 cm. A single case in Group A and Group C underwent biopsy (12.5%), and 1 case of fibrous dysplasia in Group B underwent sufficient orbit decompression (6.25%). The remaining 13 cases underwent gross total tumor resection (81.25%). No cerebral-spinal fluid leak or infection occurred. And no cosmetic problems or significant complications were observed during the follow-up. As a minimally invasive technique, the eTOA has unique advantages for carefully selected skull base lesions because of its direct route, short working distance, and distinct attack angle.

Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.