The application value and improved warning criterion of D-wave monitoring in intramedullary spinal cord tumor surgery.

BACKGROUND CONTEXT: The primary treatment method for intramedullary spinal cord tumor (IMSCT) is surgical resection, but this procedure carries a significant risk of neurological damage. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for IMSCT resection. PURPOSE: The current study aimed to explore the application value of D-wave monitoring in IMSCT surgery, and tried to investigate a tailored criterion for its early warning. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: A retrospective analysis was conducted based on the data of patients who underwent IMSCT surgeries performed by the same neurosurgical team at our hospital. IONM was applied in all surgeries. According to inclusion and exclusion criteria, ultimately 90 patients were enrolled in the study. OUTCOME MEASURES: The McCormick Scale (MMS) was applied to assess the functional outcome through outpatient visits or telephone follow-up at one month and six months postoperatively. Patients with an MMS grade over II one month after surgery were considered to have newly developed postoperative motor dysfunction (PMD). If the MMS grade could be restored to I or II six months after surgery, it was defined as a short-term PMD. Otherwise, it was defined as a long-term PMD. METHODS: The predictive value of different IONM modalities, including somatosensory evoked potential (SEP), muscle motor evoked potential (MEP), and D-wave for PMD, was assessed with sensitivity, specificity, positive predictive value, negative predictive value, and subsequent logistic regression analysis. At last, the cut-off value of the D-wave amplitude reduction ratio for predicting PMD was obtained through the receiver operating characteristic (ROC) curve analysis. RESULTS: SEP showed the worst performance in predicting short-term and long-term PMD. Significant MEP changes were indicated as an independent predictive factor for short-term PMD (OR 5.062, 95% CI 1.947-13.166, p=.001), while D-wave changes were demonstrated as an independent predictor for long-term PMD (OR 339.433, 95% CI 11.337-10770.311, p=.001). The optimum cut-off value of the D-wave amplitude reduction ratio for predicting long-term PMD was 42.18%, with a sensitivity of 100% and a specificity of 93.8% (AUC=0.981, p<.001). CONCLUSIONS: D-wave monitoring showed extremely high specificity in predicting PMD compared to SEP and MEP monitoring. Moreover, the authors suggested that a D-wave amplitude reduction of over 40% during IMSCT surgery generally indicates long-term PMD for patients.

Predictive value of Blink reflex and facial corticobulbar motor evoked potential in cerebellopontine angle tumor surgery.

OBJECTIVE: The current study examined the efficacy of the facial corticobulbar motor evoked potentials (FCoMEPs) and blink reflex (BR) on predicting postoperative facial nerve function during cerebellopontine angle (CPA) tumor surgery. METHODS: Data from 110 patients who underwent CPA tumor resection with intraoperative FCoMEPs and BR monitoring were retrospectively reviewed. The association between the amplitude reduction ratios of FCoMEPs and BR at the end of surgery and postoperative facial nerve function was determined. Subsequently, the optimal threshold of FCoMEPs and BR for predicting postoperative facial nerve dysfunction were determined by receiver operating characteristic curve analysis. RESULTS: Valid BR was record in 103 of 110 patients, whereas only 43 patients successfully recorded FCoMEP in orbicularis oculi muscle. A reduction over 50.3% in FCoMEP (O. oris) amplitude was identified as a predictor of postoperative facial nerve dysfunction (sensitivity, 77.1%; specificity, 83.6%). BR was another independent predictor of postoperative facial nerve deficit with excellent predictive performance, especially eyelid closure function. Its optimal cut-off value for predicting long-term postoperative eyelid closure dysfunction was was 51.0% (sensitivity, 94.4%; specificity, 94.4%). CONCLUSIONS: BR can compensate for the deficiencies of the FCoMEPs. The combination of BR and FCoMEPs can be used in CPA tumor surgery. SIGNIFICANCE: The study first proposed an optimal cut-off value of BR amplitude deterioration (50.0%) for predicting postoperative eyelid closure deficits in patients undergoing CPA tumor surgery.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients.

Purpose: The hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. Methods: A retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. Results: A new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). Conclusion: In the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

Luteolin-7-O-ß-d-glucuronide Ameliorates Cerebral Ischemic Injury: Involvement of RIP3/MLKL Signaling Pathway.

Luteolin-7-O-ß-d-glucuronide (LGU) is a major active flavonoid glycoside compound that is extracted from Ixeris sonchifolia (Bge.) Hance, and it is a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the neuroprotective effect of LGU was investigated in an oxygen glucose deprivation (OGD) model and a middle cerebral artery occlusion (MCAO) rat model. In vitro, LGU was found to effectively improve the OGD-induced decrease in neuronal viability and increase in neuronal death by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) leakage rate assay, respectively. LGU was also found to inhibit OGD-induced intracellular Ca2+ overload, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) decrease. By Western blotting analysis, LGU significantly inhibited the OGD-induced increase in expressions of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Moreover, molecular docking analysis showed that LGU might bind to RIP3 more stably and firmly than the RIP3 inhibitor GSK872. Immunofluorescence combined with confocal laser analyses disclosed that LGU inhibited the aggregation of MLKL to the nucleus. Our results suggest that LGU ameliorates OGD-induced rat primary cortical neuronal injury via the regulation of the RIP3/MLKL signaling pathway in vitro. In vivo, LGU was proven, for the first time, to protect the cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model, as shown by improved neurological deficit scores, infarction volume rate, and brain water content rate. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.

Depletion of regulatory T cells enhancing the anti-tumor effect of in situ vaccination in solid tumors.

The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the clinical treatment for tumor. However, the low response rate of ICIs remains the major obstacle for curing patients and effective approaches for patients with primary or secondary resistance to ICIs remain lacking. In this study, immune stimulating agent unmethylated CG-enriched (CpG) oligodeoxynucleotide (ODN) was locally injected into the tumor to trigger a robust immune response to eradicate cancer cells, while anti-CD25 antibody was applied to remove immunosuppressive regulatory T cells, which further enhanced the host immune activity to attack tumor systematically. The combination of CpG and anti-CD25 antibody obtained notable regression in mouse melanoma model. Furthermore, rechallenge of tumor cells in the xenograft model has resulted in smaller tumor volume, which demonstrated that the combinational treatment enhanced the activity of memory T cells. Remarkably, this combinational therapy presented significant efficacy on multiple types of tumors as well and was able to prevent relapse of tumor partially. Taken together, our combinational immunotherapy provides a new avenue to enhance the clinical outcomes of patients who are insensitive or resistant to ICIs treatments.

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.

For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.

Roegneria yenchiana: A new species in the Triticeae (Poaceae) from the Hengduan Mountain region.

Roegneria yenchiana sp. nov. (Triticeae) is a new species collected from Shangri-la of Yunnan Province in China based on morphological, cytological, and molecular data. It is morphologically characterized by one spikelet per node, rectangular glums, awns flanked by two short mucros in lemmas, distinguished from other species of Roegneria. The genomic in situ hybridization results indicate that R. yenchiana is an allotetraploid, and its genomic constitution is StY. Phylogenetic analyses based on multiple loci suggested that R. yenchiana is closely related to Pseudoroegneria and Roegneria, and the Pseudoroegneria served as the maternal donors during its polyploid speciation.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

Expression of KCNN4 in adult-type diffuse gliomas and its correlations with clinicopathological features and patient prognosis.

BACKGROUND: The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas. METHODS: Demographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression. The Kaplan-Meier method and the Cox regression analysis were used to evaluate the prognostic value of KCNN4 expression. RESULTS: KCNN4 showed significantly higher expression level in glioblastoma, IDH-wildtype, followed by astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.001). Enrichment analyses and tumor-infiltrating immune cell assessments suggested that KCNN4 could involve glioma progression through extracellular regulation, affecting immune response, and modulating subcellular trafficking. At last, the Kaplan-Meier analysis showed that high KCNN4 expression was significantly correlated with poor progression-free and overall survival (p < 0.001 for both). While multivariate Cox regression analysis obtained an insignificant result. CONCLUSIONS: KCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.

Iron-electrolysis assisted anammox/denitrification system for intensified nitrate removal and phosphorus recovery in low-strength wastewater treatment.

Two iron-electrolysis assisted anammox/denitrification (EAD) systems, including the suspended sludge reactor (ESR) and biofilm reactor (EMR) were constructed for mainstream wastewater treatment, achieving 84.51±4.38 % and 87.23±3.31 % of TN removal efficiencies, respectively. Sludge extracellular polymeric substances (EPS) analysis, cell apoptosis detection and microbial analysis demonstrated that the strengthened cell lysate/apoptosis and EPS production acted as supplemental carbon sources to provide new ecological niches for heterotrophic bacteria. Therefore, NO3--N accumulated intrinsically during anammox reaction was reduced. The rising cell lysis and apoptosis in the ESR induced the decline of anammox and enzyme activities. In contrast, this inhibition was scavenged in EMR because of the more favorable environment and the significant increase in EPS. Moreover, ESR and EMR achieved efficient phosphorus removal (96.98±5.24 % and 96.98±4.35 %) due to the continued release of Fe2+ by the in-situ corrosion of iron anodes. The X-ray diffraction (XRD) indicated that vivianite was the dominant P recovery product in EAD systems. The anaerobic microenvironment and the abundant EPS in the biofilm system showed essential benefits in the mineralization of vivianite.

Oculocutaneous albinism type 4: Novel compound heterozygous mutations in the SLC45A2 gene in a Chinese case.

BACKGROUND: Oculocutaneous albinism type 4 (OCA4) is a rare autosomal recessive disorder characterized by a reduction of pigmentation in skin, hair, and eyes, and OCA4 is mainly seen in the SLC45A2 gene variants. OBJECTIVE: To report a Chinese patient suspected of oculocutaneous albinism and identify the causing mutation. METHODS: Genomic DNA was extracted from the peripheral blood samples of the patient, his parents, and elder brother. Whole exome sequencing was performed in the family, and Sanger sequencing was then used to verify the mutations. RESULTS: Compound heterozygous variants, c.1304C>A (p.S435Y) and c.301C>G (p.R101G) in SLC45A2 gene, were detected in the proband, which were inherited from his father and mother respectively. Based on the ACMG guidelines, we can interpret the c.1304C>A (p.S435Y) variant as a suspected pathogenic variant and the c.301C>G (p.R101G) variant as a clinically significant unspecified variant. The diagnosis of OCA4 is confirmed. CONCLUSION: We firstly reported this case of OCA4 with the compound heterozygous variants in the SLC45A2 gene. Our findings further enrich the reservoir of SLC45A2 mutations in OCA4.

Circular RNAs: Potential biomarkers and therapeutic targets for autoimmune diseases.

The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.

Clinical Application of Long-Pulsed 800-Nm Diode Laser Depilation Technology on Microtia Reconstruction in 965 Patients.

BACKGROUND: The issue of hair growth on reconstructed ears has been a matter of concern for both patients and surgeons, despite the notable progress made in microtia reconstruction technology in recent times. OBJECTIVE: This study aims to present the practical implementation of long-pulsed 800-nm diode laser depilation technology in the field of auricular reconstruction. Furthermore, it seeks to establish a comprehensive and standardized protocol for utilizing lasers in the reconstruction of microtia ears. METHODS: A total of 965 patients (comprising 1021 ears) diagnosed with congenital microtia underwent treatment using 800-nm long-pulsed diode laser depilation. The participants received 1-3 treatment sessions with intervals of 25-30 days. To assess the effectiveness of the treatment, two independent observers compared photographs and measured the reduction in terminal hair count before and after the final session. Clinical outcomes were evaluated using VAS questionnaires, and any adverse events were diligently recorded. RESULTS: The findings indicated that the utilization of the long-pulsed 800-nm diode laser was both safe and efficient in achieving hair removal during microtia ear reconstruction. As additional sessions were conducted, pain scores demonstrated a decline, while adverse reactions remained minimal. LIMITATIONS: This is a retrospective single-institution study. CONCLUSION: The application of a long-pulsed 800-nm diode laser has been proved to be a safe and effective method for removing hair during the process of microtia ear reconstruction, involving the use of a tissue expander and autologous costal cartilage. To achieve satisfactory results in hair removal, it was found necessary to repeat the shots procedure two to three times. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Effect of Lanthanum (III) Nitrate on the Osteogenic Differentiation of Mice Bone Marrow Stromal Cells.

To study the species of lanthanum (III) nitrate (La[NO3]3) dispersed in cell media and the effect on the osteoblast differentiation of bone marrow stroma cells (BMSCs). Different La-containing precipitations were obtained by adding various concentrations of La(NO3)3 solutions to Dulbecco's modified Eagle medium (DMEM) or DMEM with fetal bovine serum (FBS). A series of characterisation methods, including dynamic light scattering, scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and protein quantification were employed to clarify the species of the different La-containing precipitations. The primary BMSCs were isolated, and the cell viability, alkaline phosphatase activity, and the formation of a mineralised nodule of BMSCs were tested when treated with different La-containing precipitations. The La(NO3)3 solutions in DMEM could form LaPO4, which exits in the particle formation, while the La(NO3)3 solutions in DMEM with FBS could form a La-PO4-protein compound. When treated with La(NO3)3 solutions in DMEM, the cell viability of the BMSCs was inhibited at the concentrations of 1, 10, and 100 µM at 1 day and 3 days. Meanwhile, the supernatant derived from the La(NO3)3 solutions in DMEM did not affect the cell viability of the BMSCs. In addition, the precipitate derived from the La(NO3)3 solutions in DMEM added to the complete medium inhibited the cell viability of the BMSCs at concentrations of 10 µM and 100 µM. When treated with La(NO3)3 solutions in DMEM with FBS, the derived precipitate and supernatant did not affect the cell viability of the BMSCs, except for the concentration of 100 µM La(NO3)3. The La-PO4-protein formed from the La(NO3)3 solutions in DMEM with FBS inhibited the osteoblast differentiation of BMSCs at the concentration of 1 µM La(NO3)3 (P < 0.05) but had no effect on either the osteoblast differentiation at the concentrations of 0.001 and 0.1 µM or on the formation of a mineralised nodule at all tested concentrations of La(NO3)3. Overall, La(NO3)3 solutions in different cell culture media could form different La-containing compounds: La-PO4 particles (in DMEM) and a La-PO4-protein compound (in DMEM with FBS). The different La-containing compounds caused different effects on the cell viability, osteoblast differentiation, and the formation of a mineralised nodule of the BMSCs. The La-containing precipitation inhibited the osteoblast differentiation by inhibiting the expression of osteoblast-related genes and proteins, providing a theoretical basis for clinical doctors to apply phosphorus-lowering drugs such as lanthanum carbon.

Complications of Injected Exogenous Growth Factor for Cosmetic Facial Rejuvenation: A Case Series and Sequential Therapy.

BACKGROUND: Exogenous growth factor presents promising soft tissue regeneration, but the complications from injectable exogenous growth factor seem to be growing. However, there is no detailed summary of complications and sequential treatment protocols. It is noted that the injection of exogenous growth factor into the soft tissue is an unreasonable or even illegal procedure, which could cause uncontrollable tissue growth and some other complications. METHODS: A total of 65 patients underwent analysis retrospectively for complications related to the injection of exogenous growth factor from 2017to 2022 at Xijing Hospital in China. Initially the symptoms mainly consisted of redness, skin temperature arisen, itching, tissue hypertrophy, localized swelling, mass, and lump, with later manifestations including ulcerations and purulent discharge. A comprehensive treatment scheme was formulated based on the location and size of the lumps as well as the type of complication. Post-treatment satisfaction was evaluated over a mean 16-month follow-up (range 6-39 months). RESULTS: A total of 65 patients participated in the treatment. Drug injection therapy was initially performed on all patients. If injections were not effective, surgical treatment (debridement/excision/liposuction) was performed. Twenty-eight patients were managed with intralesional injections alone. Patients reported improved satisfaction in 23 cases (82.14%), full symptom resolution in 3 cases (10.72%), and no improvement in 2 cases (7.14%). Surgery was required for 37 patients. Postoperative improved satisfaction was reported in 30 cases (81.08%), full symptom resolution was recorded in 4 cases (10.82%), and no improvement was seen in 3 cases (8.10%). CONCLUSIONS: This study highlights the management of complications arising from exogenous growth factor injections through the implementation of a sequential therapy approach. Specifically, this approach involves the initial administration of drug injection therapy, and if drug injection therapy proves ineffective, then surgical treatment is pursued. In conclusion, the injection of exogenous growth factors into soft tissues should be forbidden. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

ZYZ384 suppresses the growth of EGFR-mutant non-small cell lung cancer by activating JNK/MAPK signaling pathway.

The emergency of tyrosine kinase inhibitors has remarkably enhanced the clinical outcomes of cancer therapy, especially the use of EGFR inhibitors for non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable after 8-12 months treatment. New agents or treatments are urgently required to resolve this problem. In this study, we identified that compound ZYZ384 can selectively inhibit the growth of gefitinib-resistant (G-R) lung cancer cells, without affecting that of normal lung epithelial cells. ZYZ384 induced G2 arrest in G-R NSCLC cells, decreasing the expression of Cyclin B1 and increasing the expression of P21. Meanwhile, ZYZ384 also induced apoptosis in NSCLC cells and correspondingly increased the expression of cleaved Caspase 3, 8, and 9 proteins. The expression of p-JNK, p-P38, and p-ERK were also increased in H1975 NSCLC cells treated with ZYZ384. Finally, we observed that the JNK inhibitor effectively reversed the pro-apoptotic effect of ZYZ384. In conclusion, ZYZ384 is a potential therapeutic agent to inhibit the growth of NSCLCs with EGFR mutations through activating JNK, which will help the development of related anticancer drugs.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

[Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway].

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

Efficacy of intraoperative visual evoked potential amplitude reduction in predicting visual outcome after extended endoscopic endonasal resection of craniopharyngiomas.

OBJECTIVE: Postoperative visual outcome is a major concern of neurosurgeons for patients with craniopharyngiomas. The current study aimed to investigate the value of visual evoked potential (VEP) amplitude reduction (N75-P100 and P100-N145) for predicting postoperative visual dysfunction (POVD) and refining current warning criteria for VEP monitoring. METHODS: Data from 96 patients who underwent the extended endoscopic endonasal approach for craniopharyngiomas between October 2020 and November 2021 were retrospectively reviewed. VEP amplitude reduction ratios were calculated and compared between patients with POVD and those without. Subsequently, the critical threshold values of VEP amplitude reduction ratios for predicting POVD were obtained through receiver operating characteristic curve analysis. Finally, multivariate binary logistic regression analysis was applied to evaluate the effect of potential factors on the probability of experiencing POVD. RESULTS: Both N75-P100 and P100-N145 amplitude reduction ratios were significantly higher in patients with POVD (p < 0.001 for both). The threshold value of the N75-P100 amplitude reduction ratio for predicting POVD was 51.76% with an area under the curve (AUC) of 0.816 (p < 0.001), while the threshold value of the P100-N145 amplitude reduction ratio was 38.80% with an AUC of 0.738 (p < 0.001). Both N75-P100 and P100-N145 amplitude reduction ratios were identified as independent predictors for POVD via multivariate analysis (p < 0.001 and p = 0.018, respectively). CONCLUSIONS: Both N75-P100 and P100-N145 amplitude reduction ratios showed great potential to be indicators for POVD in patients with craniopharyngiomas. Regarding warning criteria for VEP monitoring, the authors recommend that both N75-P100 and P100-N145 amplitude reduction should be considered, with early warning criteria of a 50% reduction for N75-P100 amplitude and/or a 40% reduction for P100-N145 amplitude.

The Utility of Motor Evoked Potential Monitoring for Predicting Postoperative Motor Deficit in Patients With Insular Gliomas.

PURPOSE: Motor evoked potential (MEP) monitoring has been widely applied in various neurosurgical operations. This study aimed to assess the predictive value of MEP monitoring for postoperative motor deficit (PMD) in patients with insular gliomas. METHODS: Demographic and clinical data, MEP monitoring data, and follow-up data of 42 insular glioma patients were retrospectively reviewed, and 40 patients were finally enrolled. The value of MEP monitoring for predicting PMD was assessed with sensitivity, specificity, and false-positive/false-negative rates. Binary multivariate logistic regression analysis was performed to further identify the predictive value of MEP monitoring. RESULTS: Statistical analysis showed that irreversible MEP changes, but not all MEP changes, were more effective in predicting PMD. The sensitivity and specificity of irreversible MEP changes for predicting long-term PMD were 85.71 and 93.94%, whereas the false-positive and -negative rates were 25.00 and 3.12% respectively. In addition, irreversible MEP changes were identified as the only independent predictor for long-term PMD (odds ratio, 101.714; 95% confidence interval, 6.001-1724.122; p = 0.001). CONCLUSIONS: MEP monitoring has been proven to be feasible in insular glioma surgery. Irreversible MEP changes showed good performance in predicting PMD. Their absence can offer an optimistic expectation for the long-term motor outcome. The findings can provide the surgical team with a more effective interpretation of MEP changes and contribute to exploring tailored MEP warning criteria.