Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Background: Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Study on the Underlying Mechanism of Yinhua Gout Granules in the Treatment of Gouty Arthritis by Integrating Transcriptomics and Network Pharmacology.

Purpose: Yinhua Gout Granules (YGG) is a traditional Chinese medicine preparation with a variety of pharmacological effects, and its clinical efficacy in the treatment of gouty arthritis (GA) has been fully confirmed. However, the pharmacodynamic basis of YGG and its anti-inflammatory mechanism of action in GA are unknown. The objective of this study was to identify the active components and molecular mechanisms of YGG in the treatment of GA. Methods: Ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) and network pharmacology were used to identify and predict the potential active ingredients and related signaling pathways. Then, we revealed the anti-GA effects of YGG based on pharmacodynamic experiments in GA rats. Finally, we integrated transcriptomics and network pharmacology to elucidate the potential mechanism of action and verified the putative mechanism by molecular docking, immunohistochemical (IHC) and Western blot. Results: We have identified 10 major active components of YGG that may have anti-GA effects, such as ferulic acid, rutin, luteolin, etc. Using molecular docking, we found that 10 major compounds could bind well to TNF, PTGS2, IL-6, IL1ß, NOS2 and PTGS1, and the binding energies were all less than -5 kcal/mol. Animal studies have shown that YGG can improve joint inflammation and inflammatory cell infiltration, reduce serum UA, BUN and Cr levels (p<0.01), and decrease IL-1ß, IL-6, TNF-α, COX-2 and PGE2 levels in synovial tissue (p<0.01), which are associated with the pathogenesis of GA. IHC and Western blot results showed that YGG could regulate TLR4/MYD88/NF-κB pathway to inhibit the inflammatory response induced by GA. Conclusion: This study found that YGG could not only improve the disease of GA by inhibiting the production of UA in the body, but also target the regulation of TLR4/MYD88/NF-κB signaling pathway through a variety of active components to achieve effective therapeutic effects on GA.

I2 Catalyzed and TBHP/Ammonium-Promoted Conversion of Arylethanone to Nitriles via ß-Scission of Iminyl Radicals.

Herein, we report a general I2-catalyzed and TBHP/ammonium-promoted conversion of arylethanone to aromatic nitriles under air. This procedure proceeded with the ß-scission of iminyl radical, which was facilitated via quenching the released alkyl radical by tert-butyl peroxyl radical leading to peroxide followed with Kornblum-DeLaMare rearrangement. A series of aryl methyl ketone and alkyl aryl ketone worked well with good functional group tolerance in high yields. As such, this metal-free procedure represents a facile, safe, green, and practical procedure in conversion of arylethanone to aromatic nitriles.

The role of perioperative sedative anesthetics in preventing postoperative delirium: a systematic review and network-meta analysis including 6679 patients.

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.

Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy.

Background: Some studies of dual-targeted therapy (DTT) targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) have shown promising efficacy in non-small-cell lung cancer (NSCLC). Consequently, patient management following DTT resistance has gained significance. However, the underlying resistance mechanisms and clinical outcomes in these patients remain unclear. Objectives: This study aimed to delineate the molecular characteristics and survival outcomes of patients with NSCLC harboring EGFR mutations and acquired MET amplification after developing resistance to DTT. Design: We conducted a retrospective analysis of patients with NSCLC with EGFR mutations and acquired MET amplification who exhibited resistance to EGFR/MET DTT. Methods: Next-generation sequencing (NGS) was performed on patients with available tissue samples before and/or after the development of resistance to DTT. Stratified analyses were carried out based on data sources and subsequent salvage treatments. Univariate/multivariate Cox regression models and survival analyses were employed to explore potential independent prognostic factors. Results: The study included 77 NSCLC patients, with NGS conducted on 19 patients. We observed many resistance mechanisms, including EGFR-dependent pathways (4/19, 21.1%), MET-dependent pathways (2/19, 10.5%), EGFR/MET co-dependent pathways (2/19, 10.5%), and EGFR/MET-independent resistance mechanisms (11/19, 57.9%). Post-progression progression-free survival (pPFS) and post-progression overall survival (pOS) significantly varied among patients who received the best supportive care (BSC), targeted therapy, or chemotherapy (CT), with median pPFS of 1.5, 3.9, and 4.9 months, respectively (p = 0.003). Median pOS were 2.3, 7.7, and 9.2 months, respectively (p < 0.001). The number of treatment lines following DTT resistance and the Eastern Cooperative Oncology Group performance status emerged as the independent prognostic factors. Conclusion: This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.

The pertinence of gastric cancer and interleukin 10-819 single nucleotide polymorphisms: a meta-analysis and systematic review.

PURPOSE: Cytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter-819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10-819 by meta-analysis via five statistical models. METHODS: Databases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary. RESULTS: Eventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer. CONCLUSIONS: In our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.

Effectiveness of bevacizumab in the treatment of metastatic colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the benefit of bevacizumab under the comprehensive treatment strategy and its advantages over other drugs, so as to provide reference for the formulation of clinical plans. METHODS: As of October 1, 2022, the randomized controlled clinical trials of bevacizumab in combination with metastatic colorectal cancer published in PubMed, Cochrane Library and Medline databases were searched. The odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the short-term disease control effect and long-term survival of the treatment strategy. RESULTS: 21 RCTs (6665 patients; 3356 patients in the experimental group and 3309 patients in the control group; average age, 55-75 years) were treated with bevacizumab as the experimental group for metastatic colorectal cancer. BEV has stronger anti-tumor activity than the single treatment scheme (OR = 1.30, 95% CI: 1.11-1.52). And Benefits of the BEV group were 0.73 (0.55, 0.96), 1.26 (0.71, 2.24), 1.63 (0.92, 2.87) and 0.07 (0.02, 0.25) compared with CET, VAN, CED and PAN respectively. The disease control of BEV combined therapy was better (OR = 1.36, 95% CI: 1.04-1.78). The same as compared with cediranib (OR = 1.94, 95% CI: 1.06-3.55). However, the long-term prognosis of BEV, including the overall survival (HRs = 0.98, 95% CI: 0.84-1.15) and progression-free survival (HRs = 1.05,95% CI: 0.97-1.13) were not prolonged. The survival benefits of cetuximab and panitumumab were not reflected. CONCLUSION: The addition of BEV can enhance the anti-tumor ability and disease control, while cetuximab and panitumumab may have stronger ability. However, it did not effectively improve the survival of patients. A more reasonable and effective treatment plan needs more clinical experimental support.

The complete chloroplast genome of Chrysoglossum ornatum (Epidendroideae, Orchidaceae) and its phylogenetic analysis.

Chrysoglossum ornatum Blume, the type species of Chrysoglossum Blume, belongs to the tribe Collabieae of the subfamily Epidendroideae of Orchidaceae. In this study, we sequenced, assembled, and analyzed the complete chloroplast genome of C. ornatum. The result showed that the complete chloroplast genome of C. ornatum was 158,175 bp in size, consisting of a large single-copy (LSC) region of 87,235 bp, a small single-copy (SSC) region of 18,384 bp, and a pair of inverted repeats (IRs) of 26,278 bp. The chloroplast genome encoded 113 unique genes, comprising 80 protein-coding genes, 29 tRNA genes, and four rRNA genes. Phylogenetic analysis inferred from the complete chloroplast genome indicated that Chrysoglossum was closely related to Collabium Blume. This study provides genomic resources helpful for further phylogenetic and biodiversity research on Chrysoglossum.

Protective effect of FXN overexpression on ferroptosis in L-Glu-induced SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disease. However, the pathogenesis remains unclear. Recently, an increasing number of studies have demonstrated that ferroptosis is a new type of iron-dependent programmed cell death, contributes to the death of nerve cells in AD. By controlling iron homeostasis and mitochondrial function, the particular protein called frataxin (FXN), which is situated in the mitochondrial matrix, is a critical regulator of ferroptosis disease. It is encoded by the nuclear gene FXN. Here, we identified a novel underlying mechanism through which ferroptosis mediated by FXN contributes to AD. METHODS: Human neuroblastoma cells (SH-SY5Y) were injured by L-glutamate (L-Glu). Overexpression of FXN by lentiviral transfection. In each experimental group, we assessed the ultrastructure of the mitochondria, the presence of iron and intracellular Fe2 + , the levels of reactive oxygen species, the mitochondrial membrane potential (MMP), and lipid peroxidation. Quantification was done for malondialdehyde (MDA) and reduced glutathione (GSH), as well as reactive oxygen species (ROS). Western blot and cellular immunofluorescence assays were used to detect the expression of xCT and GPX4 proteins which in System Xc-/GPX4 pathway, and the protein expressions of ACSL4 and TfR1 were investigated by Western blot. RESULTS: The present work showed: (1) The expression of FXN was reduced in the L-Glu group; (2) Compared with the Control group, MMP was reduced in the L-Glu group, and mitochondria were observed to shrink and cristae were deformed, reduced or disappeared by transmission electron microscopy, and after FXN overexpression and ferrostatin-1 (Fer-1) (10 µmol/L) intervened, MMP was increased and mitochondrial morphology was significantly improved, suggesting that mitochondrial function was impaired in the L-Glu group, and overexpression of FXN could improve the manifestation of mitochondrial function impairment. (3) In the L-Glu group, ROS, MDA, iron ion concentration and Fe2+ levels were increased, GSH was decreased. Elevated expression of ACSL4 and TfR1, important regulatory proteins of ferroptosis, was detected by Western blot, and the expression of xCT and GPX4 in the System Xc-/GPX4 pathway was reduced by Western blot and cellular immunofluorescence. However, the above results were reversed when FXN overexpression and Fer-1 intervened. CONCLUSION: To conclude, our research demonstrates that an elevated expression of FXN effectively demonstrates a robust neuroprotective effect against oxidative damage induced by L-Glu. Moreover, it mitigates mitochondrial dysfunction and lipid metabolic dysregulation associated with ferroptosis. FXN overexpression holds promise in potential therapeutic strategies for AD by inhibiting ferroptosis in nerve cells and fostering their protection.

Pyridine-catalyzed ring-opening reaction of cyclopropenone with bromomethyl carbonyl compounds toward furan-2(5H)-ones.

We developed a pyridine-catalyzed annulation of diaryl cyclopropenone with bromomethyl carbonyl compounds leading to 5-carbonyl furan-2(5H)-ones. Pyridinium, derived from the reaction of bromomethyl carbonyl and pyridine, triggered the reaction by the inter-molecular Michael addition to cyclopropenone. This procedure was sensitive neither to air nor moisture and proceeded at room temperature with broad substrate scopes and good functional group tolerance in moderate-to-good yields. As such, it represents a facile and practical pathway leading to 5-carbonyl furan-2(5H)-one derivatives.

Comparative severe dermatologic toxicities of immune checkpoint inhibitors in malignant melanoma: A systematic review and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have advanced the therapeutic landscape for malignant melanoma patients. However, they can cause permanent and irreversible dermatologic immune-related adverse events (irAEs) that may lead to interruption of ICI treatment or become life-threatening. To assess the risk of severe dermatologic irAEs (grade 3 or higher) among ICIs for advanced melanoma, we conducted a network meta-analysis (NMA). METHODS: Phase II/III randomized controlled clinical trials (RCTs) involving ICIs were retrieved from various databases, including PubMed, Embase, Cochrane Library, and Web of Science. These trials were published from the inception of databases to October 15, 2022. In addition, the risk of severe dermatologic irAEs associated with ICI types and doses was evaluated and compared by NMA. RESULTS: This study included 20 Phase II/III RCTs with a total of 10 575 patients. The results indicated that ICIs carry a higher risk of severe dermatologic irAEs compared to chemotherapy. Additionally, the combinational therapy of Nivolumab + Ipilimumab was associated with a higher risk than ICI monotherapy. Comparatively, the latest treatment option involving dual ICI therapy with Relatlimab + Nivolumab showed a lower toxicity risk, but higher than Ipilimumab alone. Lastly, Nivolumab, at a dose of 3 mg/kg every 2 weeks, was observed as the lowest-risk dosing regimen for severe dermatologic irAEs in patients with advanced melanoma. CONCLUSION: The findings suggest that Nivolumab (1 mg/kg) + Ipilimumab (3 mg/kg) administered every 3 weeks should be used cautiously in patients with advanced melanoma at high risk for dermatologic irAEs. While we recommend the preferred regimen of Nivolumab (dose = 3 mg/kg, every 2 weeks).

Oxidative Stress-related Signaling Pathways in Lung Cancer and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Lung cancer has the highest incidence and mortality rate among all cancers in China， with its complex and variable nature， long treatment duration， and often poor prognosis. Currently， the treatment of lung cancer mainly employs classical therapies such as surgery， radiotherapy， and chemotherapy， but some patients may experience a series of adverse reactions， which affect their quality of life， survival period， and treatment outcomes. As reported， oxidative stress is one of the important pathogenic factors of lung cancer， affecting its occurrence and development. Oxidative stress is a state of imbalance between oxidative products and antioxidant defense mechanisms in the body. The intervention of oxidative stress in the occurrence and development of lung cancer is related to multiple signaling pathways， including the Kelch-like ECH-associated protein 1 （Keap1）-nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and nuclear factor-κB （NF-κB） signaling pathway. Currently， researchers in China and abroad have conducted extensive studies on the occurrence and development of lung cancer and the pathophysiological mechanisms of drug intervention. The results have shown that oxidative stress plays an important role in the occurrence and development of lung cancer. Chinese medicine monomers and compounds can regulate oxidative stress levels and intervene in related signaling pathways， thereby inhibiting or delaying the occurrence and development of lung cancer. Based on this， this article mainly summarized the relevant signaling pathways regulating oxidative stress intervention in lung cancer in recent years， and also reviewed the latest research on Chinese medicine monomers and compounds in regulating oxidative stress to treat lung cancer， aiming to provide new ideas for research on drug treatment of lung cancer and clinical drug development， as well as to provide references and guidance for further in-depth mechanistic studies in the future.

Research progress of KRAS inhibitors / 中国药科大学学报

@#Abstract: KRAS protein, a small GTPase encoded by the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene, is involved in cell proliferation, differentiation, migration and cell survival, and is known as a regulatory switch for the cell life cycle. However, KRAS gene is prone to mutation, leading to hyperactivation of its downstream signaling pathways, and has a vital role in driving tumorigenesis. KRAS mutations predominantly take place at residue G12, G13 or Q61, and different mutants have varying effects on protein physiological functions and tumor types. Due to its smooth surface and high affinity for nucleotides, KRAS had been considered to be “undruggable” until the launch of selective KRAS G12C inhibitors sotorasib and adagrasib, which broke the dogma. This review introduces the structure and functions of KRAS, as well as the status and progress of inhibitors directly targeting KRAS mutants (G12C, G12D, G12R, G12S) and pan-KRAS inhibitors, aiming to provide some insightful reference for the development of KRAS inhibitors.

Effect of volatile oil of Ligusticum chuanxiong on transdermal properties and cytotoxicity of triptolide in vitro / 中国药房

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Autoimmune glial fibrillary acidic protein astrocytopathy complicated with low flow perimedullary arteriovenous fistula: a case report.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy and low-flow perimedullary arteriovenous fistulas (PMAVFs) may cause longitudinal widespread myelopathy. We report a middle-aged male patient with autoimmune GFAP astrocytopathy complicated with low flow PMAVFs disease, presenting with lower extremity weakness and dysuria. Magnetic resonance imaging (MRI) of the spinal cord revealed a significant longitudinal extent of T2 high signal from T11 to L1, with the lesion located proximal to the vascular territory supplied by the anterior spinal artery. Multiple patchy abnormal signals were seen adjacent to the anterior and posterior horns of the lateral ventricles bilaterally and at the centers of the semi-ovals on MRI of the cranial brain, with iso signal in T1Flair, the high signal in T2WI, and no high signal seen in Diffusion Weighted Imaging (DWI). Subsequently, the presence of anti-GFAP antibodies was detected in the cerebrospinal fluid (CSF), and the diagnosis of autoimmune GFAP astrocytopathy in conjunction with low-flow PMAVFs was confirmed through spinal digital subtraction angiography (DSA). This case report aims to increase neurologists' awareness of this disease and avoid missed or misdiagnosed cases that may lead to delayed treatment.

Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) stands as a rare and locally aggressive soft tissue tumor, characterized by intricated molecular alterations. The imperative to unravel the complexities of intratumor heterogeneity underscores effective clinical management. Herein, we harnessed single-cell RNA sequencing (scRNA-seq) to conduct a comprehensive analysis encompassing samples from primary sites, satellite foci, and lymph node metastases. Rigorous preprocessing of raw scRNA-seq data ensued, and employing t-distributed stochastic neighbor embedding (tSNE) analysis, we unveiled seven major cell populations and fifteen distinct subpopulations. Malignant cell subpopulations were delineated using infercnv for copy number variation calculations. Functional and metabolic variations of diverse malignant cell populations across samples were deciphered utilizing GSVA and the scMetabolism R packages. Additionally, the exploration of differentiation trajectories within diverse fibroblast subpopulations was orchestrated through pseudotime trajectory analyses employing CytoTRACE and Monocle2, and further bolstered by GO analyses to elucidate the functional disparities across distinct differentiation states. In parallel, we segmented the cellular components of the immune microenvironment and verified the presence of SPP1+ macrophage, which constituted the major constituent in lymph node metastases. Remarkably, the CellChat facilitated a comprehensive intercellular communication analysis. This study culminates in an all-encompassing single-cell transcriptome atlas, propounding novel insights into the multifaceted nature of intratumor heterogeneity and fundamental molecular mechanisms propelling metastatic DFSP.

Neottiamaolanensis, a replacement name for Neottiabifida M.N.Wang (Orchidaceae).

According to Articles 53.1 of the International Code of Nomenclature for Algae, Fungi, and Plants (Shenzhen Code), Neottiabifida M.N.Wang (as 'bifidus'; PhytoKeys 229: 222, 2023) is an illegitimate name, and hence a new name Neottiamaolanensis M. N. Wang is proposed here.