Association of Nirmatrelvir/Ritonavir Treatment on Upper Respiratory Severe Acute Respiratory Syndrome Coronavirus 2 Reverse Transcription-Polymerase Chain Reaction (SARS-Cov-2 RT-PCR) Negative Conversion Rates Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Acceleration of negative respiratory conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. METHODS: A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between 5 March and 5 April 2022. The time from positive to negative upper respiratory reverse transcription-polymerase chain reaction (RT-PCR) conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients' baseline demographic and clinical characteristics. RESULTS: There were 258 patients treated with nirmatrelvir/ritonavir and 224 nontreated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in nontreated patients. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and nontreated patients, corresponding to a hazard ratio of 4.33 (95% confidence interval, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients' baseline characteristics. CONCLUSIONS: This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.

Phage nanoparticle as a carrier for controlling fungal infection.

A mass of nanocarriers have been exploited and utilized for prevention of fungi, including organic nanomaterials, inorganic nanoparticles, polypeptides, and viruses. Due to biological safety and flexible genetic engineering property, bacteriophages, as bionanoparticles, are widely used in the diagnosis and treatment of microorganisms, which can be easily loaded with proteins and drugs. In particular, random DNAs can be inserted into the genome of phage by phage display technology, and it is possible to obtain the peptide/antibody targeting fungi from phage library. Meanwhile, phages displaying specific peptides are able to conjugate with other nanoparticles, which have both characteristics of peptides and nanomaterials, and have been used for precise detection of fungi. Additionally, phage nanomaterials as carriers can reduce the toxicity of drugs, increase the time of drug circulation, stimulate the immune response, and have an anti-fungal effect by itself. In this review, we summarize the recent applications of bacteriophages on the study of fungi. The improvement of our understanding of bacteriophage will supply new tools for controlling fungal infections. These phage libraries were used to pan the specific peptides for diagnosis, prevention, and treatment of fungi. KEY POINTS: • System fungal infection has no significant clinical symptoms; it is important to develop vaccine, diagnosis, and therapeutic agents to reduce mortality; phage is an ideal carrier for vaccine and drug to stimulate immune response and improve the efficiency of drug, and also can improve the sensitivity of detection • This review summarized recent studies on phage-based fungal vaccine and threw light on the developing therapeutic phage in the treatment of fungal infection.

Changes in Hippocampal Plasticity in Depression and Therapeutic Approaches Influencing These Changes.

Depression is a common neurological disease that seriously affects human health. There are many hypotheses about the pathogenesis of depression, and the most widely recognized and applied is the monoamine hypothesis. However, no hypothesis can fully explain the pathogenesis of depression. At present, the brain-derived neurotrophic factor (BDNF) and neurogenesis hypotheses have highlighted the important role of plasticity in depression. The plasticity of neurons and glial cells plays a vital role in the transmission and integration of signals in the central nervous system. Plasticity is the adaptive change in the nervous system in response to changes in external signals. The hippocampus is an important anatomical area associated with depression. Studies have shown that some antidepressants can treat depression by changing the plasticity of the hippocampus. Furthermore, caloric restriction has also been shown to affect antidepressant and hippocampal plasticity changes. In this review, we summarize the latest research, focusing on changes in the plasticity of hippocampal neurons and glial cells in depression and the role of BDNF in the changes in hippocampal plasticity in depression, as well as caloric restriction and mitochondrial plasticity. This review may contribute to the development of antidepressant drugs and elucidating the mechanism of depression.

Familial arachnoid cysts: a review of 35 families.

INTRODUCTION: Arachnoid cysts are commonly considered congenital lesions, but this has not been proven. With the development of neuroimaging and DNA testing technology, more cases of familial arachnoid cysts have been reported. Herein, we review such cases. MATERIALS AND METHODS: The PubMed, Embase, and Web of Science databases were searched for case reports of arachnoid cysts published through April 2018. Case reports were included only if two or more related patients were diagnosed with an arachnoid cyst by neuroimaging or intraoperatively. For each report, the following data were extracted: first author name, date of publication, number of families, number of patients, location of the arachnoid cysts, patient age, patient sex, and genetic mutations and associated disease. RESULTS: Our searches identified 33 case reports involving 35 families and 115 patients. The locations of arachnoid cysts were similar in 25 of the 35 families. Spinal extradural arachnoid cysts were reported most often, followed by arachnoid cysts in the middle fossa and posterior fossa. A left-sided predominance was noticed for arachnoid cysts of the middle fossa. Mutation of the FOXC2 gene was reported most often, and arachnoid cysts may be associated with mutations on chromosome 16. CONCLUSIONS: Although the origin of arachnoid cysts is believed to have a genetic component by some researchers, the genes associated with arachnoid cysts remain unknown. Unfortunately, the evidence remains insufficient.

Gliomas in the sellar turcica region: a retrospective study including adult cases and comparison with craniopharyngioma.

PURPOSE: Previous studies of sellar gliomas have been confined to pediatric optic pilocytic gliomas. The present study aimed to analyze the features of sellar gliomas involving both pediatric and adult patients with various pathologies and to compare them with craniopharyngiomas to better differentiate the diagnosis. METHODS: Twenty-seven sellar gliomas were retrospectively examined regarding their demographics, pathologies, clinical and imaging presentations, surgeries and postoperative complications. Thirty craniopharyngiomas from the same period and 880 gliomas of the most common pathologies from 2008-2014 were included for comparisons. RESULTS: In total, 55.6% of the sellar gliomas were adult cases. The pathology included pilocytic astrocytoma, ganglioglioma, diffuse astrocytoma, pilomyxoid astrocytoma, oligoastrocytoma, and glioblastoma. Compared with craniopharygiomas, sellar gliomas presented with a significantly lower ratio of visual disturbances, growth hormone deficiencies, lesion cystic changes, and calcification. Sellar gliomas had significantly greater effects on the patients' mentality and anatomical brain stem involvement. Total resections were achieved in 11 patients, which were significantly lower compared with craniopharyngiomas. CONCLUSIONS: Sellar gliomas affect both pediatric and adult patients with pathological changes extending beyond pilocytic astrocytomas. They have diverse clinical manifestations and imaging presentations. Differences exist regarding several aspects between sellar gliomas and craniopharyngiomas, which may facilitate a differential diagnosis.

Pituitary tumor transforming gene: a novel therapeutic target for glioma treatment.

Glioma which has strong proliferation and angiogenesis ability is the most common and malignant primary tumor in central nervous system. Pituitary tumor transforming gene (PTTG) is found in pituitary tumor, and plays important role in cell proliferation, cell cycle, cell apoptosis, and angiogenesis. However, the role of PTTG in glioma is still incompletely investigated. Here, we explored the correlation between PTTG and glioma grade, as well as micro-vessel density (MVD). In addition, siRNA was used to silence PTTG expression in glioma cell lines including U87MG, U251, and SHG44. Cell proliferation, apoptosis, invasion, and angiogenesis were studied both in vitro and in vivo. Our results demonstrated that PTTG expression was significantly up-regulated in glioma, and had positive correlation with glioma grade and MVD. Silencing of PTTG inhibited glioma cell proliferation, migration/invasion, and angiogenesis, induced cell apoptosis, suppressed cell invasion, and arrested cell cycle at G0/G1 stage. Silencing of PTTG could also inhibit tumor growth, invasion, and angiogenesis in vivo. Our data indicated that PTTG might be a potential target for glioma treatment.

Location of Pterygopalatine Fossa and its Relationships to the Structures in Sellar Region.

PURPOSE: The aim of this study is to locate pterygopalatine fossa (PPF) and the opening of its communicating canals by accessing the relationship between PFF and the endoscopic landmarks such as the tubercular recess (TR) and middle lowest point of sellar floor (SF) as well as analyze the relation between PPF and important structures such as internal carotid artery (ICA) and optic canal (OC). MATERIALS AND METHODS: Computer topographic angiography (CTA) images of 118 PPF regions were reviewed. The measurement was on coronal, sagittal, and axial planes after multiplanar reconstruction (MPR). The location of PPF and its relationship to the sphenoid sinus, ICA, and OC were studied. The communicating canals of PPF, which were related to the transsphenoid approach, were three-dimensionally measured by the stationary structures, such as the middle lowest point of SF, the sagittal midline, and the top and bottom wall of sphenoid sinus. RESULT: The posterior part of PPF was located by the middle lowest point of SF. The anterior opening of sphenopalatine foramen (SPF), pterygoid canal (PC), palatovaginal canal (PVC), and foramina rotundum (FR) have relative stationary position, which can be located by the landmarks of sellar region during the endoscopic surgery. CONCLUSIONS: Pterygopalatine fossa is related to numerous neurovascular structures. Accurate understanding of the radiologic anatomy of PPF is beneficial for the PPF disease diagnosis, the selection of treatment plan and the prognosis evaluation.

A new method of locating foramen rotundum and its anatomic study.

PURPOSE: The purpose of this study is to provide a new method to locate the foramen rotundum (FR) based on the structures in the wall of sphenoid. MATERIALS AND METHODS: Computed tomographic angiography images of 172 FR in adults and 10 bony specimens were reviewed. The measurement was on coronal, sagittal, and axial planes after multiplanar reconstruction. The diameter, length, and direction of FR were measured. The middle lowest point of sellar region, the sagittal midline, and the bottom of sphenoid sinus were selected as the landmarks to locate the FR. RESULT: The FR can be found and identified easily on computed tomographic angiography image. The bony diameter measured in CT image is in accordance with that in specimen. The anterior opening and posterior opening can be located by the stationary structures in the sphenoid sinus. CONCLUSIONS: The FR is a stationary bony structure; its length, diameter, and angle are relatively constant; and it can be easily located by the data measured in this study. The FR should be protected in the process of transsphenoid approach as well as be precisely located by the procedure about it.

Anatomic Study of Posterior Communicating Artery in Computed Tomographic Image.

PURPOSE: This study aims to provide an anatomic data of posterior communicating artery (PComA) and its anatomic relationship to the adjacent structures, so as to guide surgeons in the surgery of internal carotid artery-posterior communicating artery aneurysm clipping and sellar tumors resection without injuring the PComA. METHODS: Computer topographic angiography images of 123 individuals were reviewed, and the measurements were done on coronal, sagittal, axial, and other user-defined planes after multiplanar reconstruction. Posterior communicating artery was classified in the reconstructed three-dimensional image, measured in proper planes, and located by the structures such as anterior clinoid process (ACP), posterior clinoid process (PCP), and sagittal midline. RESULTS: Six types of PComA were identified in this study based on its existence and origin. The initial part of PComA can be located by ACP, PCP, and sagittal midline based on some particular angles and distances. CONCLUSIONS: Posterior communicating artery varies in different individuals, and the radiologic study of it is an optimal way to analyze the variances. The anatomic relations between PComA and basic skull structures such as the ACP and PCP are especially important for neurosurgeons.

Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by temperature in Caenorhabditis elegans.

In the nematode Caenorhabditis elegans, stress resistance can be regulated by dauer formation (daf) genes. In the present study, regulation of heavy metal lead (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects of varied temperatures below (15°C) or above (25 and 30°C) the presumptive optimum growth temperature (20°C). More acute toxicity of Pb, indicated by the 24-h median lethal concentrations (LC50), was observed in wild-type adults than in the daf-21 mutant adults at 15, 20 and 25°C; however, the daf-21 mutant adults showed more sensitivity at 30°C. Enhanced Pb sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with both increased and decreased temperatures when compared to that at 20°C. Additional examined endpoints included time course of toxicity at LC50s, pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective results showed that temperatures both above and below 20°C exacerbated Pb toxicity, and that the protein level of daf-21/Hsp90 was one of the most sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf-21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced toxicity in nematodes. Further, the stress responses related to Hsp90 expression in C. elegans may have considerable potential as sensitive biomarkers for the monitoring of environmental Pb contamination.

miR-125b inhibits Connexin43 and promotes glioma growth.

MicroRNA is strongly associated with tumor growth and development. This study examined the potential roles of miR-125b in glioma growth. We found that miR-125b promotes glioma cell line growth and clone formation, and protects the glioma cells from apoptosis in vitro. The miR-125b-transfected glioma cells also demonstrated increased growth after in vivo transplantation. We further identified that miR-125b inhibits Connexin43 expression, and the overexpression of Connexin43 antagonizes the effects of miR-125b in cell growth and anti-apoptosis. We conclude that miR-125b regulates glioma growth partly through Connexin43 protein.

Diagnosis and treatment status of suprasellar optic pathway cavernous malformations.

Cerebral cavernous malformations constitute a subtype of cerebral vascular malformation typically located in the cerebral cortex. However, their occurrence in the suprasellar optic pathway is relatively rare. There is some uncertainty surrounding the clinical diagnostic methods and optimal treatment strategies specific to suprasellar optic pathway cavernous malformations. In this narrative review, we retrospectively analyzed relevant literature related to suprasellar visual pathway cavernous malformations. We conducted a study involving 90 patients who were postoperatively diagnosed with cavernous malformations, including the 16-year-old male patient mentioned in this article. We have summarized crucial clinical data, including the patient age distribution, sex ratio, lesion locations, primary symptoms, and surgical approaches. The comprehensive analysis of this clinical information underscores the critical importance of timely intervention in relieving symptoms and improving neurological deficits in affected patients. These findings provide valuable guidance and insight for clinical practitioners and researchers dealing with this specific medical condition.

Advances in Brain Tumor Therapy Based on the Magnetic Nanoparticles.

Brain tumors, including primary gliomas and brain metastases, are one of the deadliest tumors because effective macromolecular antitumor drugs cannot easily penetrate the blood-brain barrier (BBB) and blood-brain tumor barrier (BTB). Magnetic nanoparticles (MNPs) are considered the most suitable nanocarriers for the delivery of brain tumor drugs because of their unique properties compared to other nanoparticles. Numerous preclinical and clinical studies have demonstrated the potential of these nanoparticles in magnetic targeting, nuclear magnetic resonance, magnetic thermal therapy, and ultrasonic hyperthermia. To further develop and optimize MNPs for the diagnosis and treatment of brain tumors, we attempt to outline recent advances in the use of MNPs to deliver drugs, with a particular focus on their efficacy in the delivery of anti-brain tumor drugs based on magnetic targeting and low-intensity focused ultrasound, magnetic resonance imaging for surgical real-time guidance, and magnetothermal and ultrasonic hyperthermia therapy. Furthermore, we summarize recent findings on the clinical application of MNPs and the research limitations that need to be addressed in clinical translation.

Effectiveness of inactivated COVID-19 vaccines against mild disease, pneumonia, and severe disease among persons infected with SARS-CoV-2 Omicron variant: real-world study in Jilin Province, China.

It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

Erratum: MicroRNA-217 inhibits cell proliferation and invasion by targeting Runx2 in human glioma.

[This corrects the article on p. 1482 in vol. 8, PMID: 27186274.].

Uncovering the Underlying Mechanisms of Ketamine as a Novel Antidepressant.

Major depressive disorder (MDD) is a devastating psychiatric disorder which exacts enormous personal and social-economic burdens. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been discovered to exert rapid and sustained antidepressant-like actions on MDD patients and animal models. However, the dissociation and psychotomimetic propensities of ketamine have limited its use for psychiatric indications. Here, we review recently proposed mechanistic hypotheses regarding how ketamine exerts antidepressant-like actions. Ketamine may potentiate α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR)-mediated transmission in pyramidal neurons by disinhibition and/or blockade of spontaneous NMDAR-mediated neurotransmission. Ketamine may also activate neuroplasticity- and synaptogenesis-relevant signaling pathways, which may converge on key components like brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) and mechanistic target of rapamycin (mTOR). These processes may subsequently rebalance the excitatory/inhibitory transmission and restore neural network integrity that is compromised in depression. Understanding the mechanisms underpinning ketamine's antidepressant-like actions at cellular and neural circuit level will drive the development of safe and effective pharmacological interventions for the treatment of MDD.

Femoral epithelioid hemangioendothelioma detected with magnetic resonance imaging and positron emission tomography/computed tomography: A case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon low-grade aggressive vascular tumor. It can occur in almost all locations, but is rarely encountered in bone. CASE SUMMARY: We report a 23-year-old man who presented with left hip pain with no obvious cause. X-ray revealed bone destruction in the left femoral neck with sclerosis at the edges of the lesions. Magnetic resonance imaging (MRI) showed bone destruction in the medullary cavity of the left femoral head and neck. 18F-deoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging showed bone destruction in the left ischium, acetabulum, and left femoral head neck, accompanied by increased radioactive uptake; the maximum standard uptake value was 4.2. Histopathologic examination revealed spindle-shaped mesenchymal tissue hyperplasia with scattered epithelioid cells. The patient underwent left femoral head replacement surgery. No signs of recurrence were observed as of the 18-mo follow-up. CONCLUSION: The definitive diagnosis of femoral EHE can be established aided by the MRI and PET/CT findings.

Incidental detection of primary hepatocellular carcinoma on 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography imaging in a patient with prostate cancer: A case report.

RATIONALE: Prostate-specific membrane antigen positron emission tomography-computed tomography (F-PSMA-1007 PET/CT) imaging is an emerging method for the diagnosis of prostate cancer (PC), but its efficiency in detecting other accompanying diseases has rarely been investigated. PATIENT CONCERNS: A 77-year-old man presented with a complaint of bone pain throughout his entire body lasting for 2 weeks. Routine preoperative whole-body bone scanning revealed multiple osteogenic metastases. His alpha-fetoprotein and prostate-specific antigen levels were 108.2 ng/mL and 53.32 ng/mL, respectively. F-PSMA-1007 PET/CT imaging revealed high tracer uptake in the primary lesion in the liver and the peripheral zone of the prostate. DIAGNOSES: Due to the results from imaging and pathological examinations, a diagnosis of PC with multiple bone metastases accompanied by primary hepatocellular carcinoma was made. INTERVENTIONS: Taking into consideration the patient's age, interventional therapy was performed for the liver lesion, whereas the prostate and bone lesions were treated with endocrine therapy. OUTCOMES: The patient recovered well and was discharged uneventfully postoperatively. The patient was also doing well at the 6-month follow-up. LESSONS: PSMA-PET/CT imaging results must be interpreted cautiously when the uptake of PSMA increases in a single lesion instead of the most common sites of PC metastasis. Pathological examination of the suspected lesions is also recommended.

Chromatin-regulating genes are associated with postoperative prognosis and isocitrate dehydrogenase mutation in astrocytoma.

BACKGROUND: Abnormality in chromatin regulation is a major determinant in the progression of multiple neoplasms. Astrocytoma is a malignant histologic morphology of glioma that is commonly accompanied by chromatin dysregulation. However, the systemic interpretation of the expression characteristics of chromatin-regulating genes in astrocytoma is unclear. METHODS: In this study, we investigated the expression profile of chromatin regulation genes in 194 astrocytoma patients sourced from The Cancer Genome Atlas (TCGA) database. The relevance of gene expression and postoperative survival outcomes was assessed. RESULTS: Based on the expression patterns of chromatin regulation genes, two primary clusters and three subclusters with significantly different survival outcomes were identified. The patients in cluster_1 (or subcluster_1) had a poorer prognosis than the other groups, and this particular cohort were older, with a more advanced grade of tumor and isocitrate dehydrogenase-wildtype distribution. Detection of the differentially expressed genes revealed that the group with poor prognosis was characterized by downregulation of H2AFY2, WAC, HDAC5, ZMYND11, TET1, SATB1, and MYST4, and overexpression of EYA4. Moreover, all eight genes were significantly correlated with overall survival (OS) in astrocytoma. Age-associated genes were investigated and the expression levels of EYA4, TET1, SATB1, WAC, ZMYND11, and H2AFY2 were found to be closely correlated with advanced age. Regression analysis suggested that the expression levels of H2AFY2, HILS1, EYA1, EYA4, and KDM5B were independently associated with IDH mutation status. The differential expressions of 34 common genes were significantly associated with age, grade, and IDH mutant. CONCLUSIONS: The study revealed that the expression pattern of chromatin regulation genes was significantly associated with postoperative prognosis in astrocytoma. Moreover, the differential expression of particular genes was strongly associated with clinical characteristics such as age, grade, and IDH subtype. These results suggest that the genes involved in chromatin regulation play important roles in the biological process of astrocytoma progression, and these molecules could potentially serve as therapeutic targets in astrocytoma.

Gender Differences in Depression: Evidence From Genetics.

Compared with men, female accounts for a larger proportion of patients with depression. Behavioral genetics researches find gender differences in genetic underpinnings of depression. We found that gender differences exist in heritability and the gene associated with depression after reviewing relevant research. Both genes and gene-environment interactions contribute to the risk of depression in a gender-specific manner. We detailed the relationships between serotonin transporter gene-linked promoter region (5-HTTLPR) and depression. However, the results of these studies are very different. We explored the reasons for the contradictory conclusions and provided some suggestions for future research on the gender differences in genetic underpinnings of depression.