Background: The hypotension prediction index (HPI) is an algorithm designed to predict hypotension. Some studies have reported that HPI-guided hemodynamic management strategies decrease intraoperative hypotension and complications; however, the effect of HPI on reducing perioperative complications is controversial. This meta-analysis aimed to assess the efficacy of the HPI in reducing major complications and intraoperative hypotension. Methods: We conducted this meta-analysis according to the PRISMA statement and Cochrane Handbook guidelines. A comprehensive literature review was conducted to identify studies focusing on the efficacy of HPI-guided management in reducing intraoperative hypotension and postoperative complications. The PubMed, Embase, Scopus, and Web of Science databases were searched, and the resulting data were combined to calculate the pooled mean differences or risk ratios (RRs) with 95% CIs of both randomized controlled trials (RCTs) and retrospective studies, as appropriate. Heterogeneity and potential publication bias were also assessed. Results: Nineteen articles (12 RCTs and 7 retrospective studies) with 2570 recruited patients were included in this meta-analysis. The critical evaluation of the study quality revealed a low risk of bias in the included RCTs. Among the non-randomized trials, one was rated 7, two were rated 8, and the remaining four were rated 9 on the Newcastle-Ottawa Scale, indicating high quality and a low risk of bias. HPI-guided management significantly reduced intraoperative hypotension and associated major complications (RR = 0.79, 95% CI [0.69–0.90], I2 = 0, P < 0.001). Blood loss and length of hospital stay were comparable between the groups. Conclusions HPI-guided management significantly reduced intraoperative hypotension and major complications.

Endotoxins are common exogenous pyrogens. Excessive endotoxins in medical devices and injections can lead to serious consequences such as sepsis, septic shock, and even death. Therefore, endotoxin detection plays a crucial role in medical, pharmaceutical, and food sectors. The wide application of Limulus amebocyte lysate (LAL) has led to a sharp decline in the number of horseshoe crabs. Moreover, the LAL assay has limitations such as interbatch variations and difficulty in quantification. The recombinant factor C (rFC) assay is stable between batches, highly sensitive, and capable of quantitation, and thus it can be used as an alternative for the LAL assay. However, the high cost and complex procedures involved in producing recombinant factor C have limited the widespread application of this method. In order to simplify the preparation and reduce the production cost of recombinant factor C, this study focuses on the production of recombinant factor C based on the baculovirus expression system. Multiple measures such as a high-yield and anti-apoptotic vector qBac-IIIG, the optimal signal peptide, and the optimized codon were used to reach the goal of endotoxin detection with cell supernatant. This method simplifies the steps of protein purification. The sensitivity of the supernatant reached 0.05 EU/mL in a 1-L fermentation system, and 500 000 detecting reactions can be supported per liter of fermentation broth. This study increases the yield and activity of recombinant factor C, simplifies the procedures of protein purification, and reduces the cost, laying a foundation for the promotion and application of recombinant factor C in endotoxin detection.
Animals ; Recombinant Proteins/genetics* ; Horseshoe Crabs/chemistry* ; Baculoviridae/metabolism* ; Endotoxins/analysis* ; Protein C/biosynthesis* ; Genetic Vectors/genetics* ; Arthropod Proteins/genetics* ; Enzyme Precursors ; Serine Endopeptidases

Objective:To investigate the impact of lesions in different nuclei of the subcortical basal ganglia on speech processing functions in patients with post-stroke dysarthria.Methods:From July 2022 to September 2023, a total of 20 patients with post-stroke dysarthria (patient group) and 22 healthy individuals (control group) were recruited. Brain imaging data, including structural magnetic resonance imaging(MRI) and diffusion-weighted imaging (DWI), as well as behavioral data of speech fluency task and picture association task were collected. Structural MRI data was analyzed using SPM12 software to perform voxel-based morphometry (VBM), measuring cortical thickness and gray matter volume (VGM) in specific nuclei of the basal ganglia. Behavioral metrics, such as reaction time (RT) and the number of valid responses were extracted for each task. Statistical analysis was conducted using SPSS 27.0 and R 4.0 softwares. Spearman correlation analysis was applied to examine relationships between neuroimaging parameters and behavioral performance indicators.Results:The patient group exhibited significantly smaller gray matter volumes in both left and right caudate nuclei((2.69±0.92)mm 3, (3.17±0.91)mm 3 ) and putamen (3.31±1.08)mm 3, (3.66±0.91)mm 3) compared to the control group (caudate nuclei (3.19±0.36)mm 3, (3.49±0.52)mm 3 putamen (4.52±0.54)mm 3, (4.72±0.64)mm 3), with statistically significant differences ( t=-2.83, 1.68; t=-3.59, 3.52, both P<0.05). Behavioral experiments revealed that the patient group exhibited significantly prolonged reaction time during picture association and naming tasks (1 910.50(1 214.25, 3 806.75) ms, 1 362.00(978.00, 2 297.00) ms) compared to the control group (1 618.00(1 162.75, 2 401.75) ms, 1 224.00(984.25, 1 661.50) ms; Z=-5.20, -4.61, both P<0.05). Gray matter volumes in the left caudate nucleus and left putamen exhibited negative correlations with reaction times during the picture naming task ( r=-0.52, -0.54, both P<0.05). Additionally, the gray matter volume of the left putamen demonstrated a positive correlation with the number of valid responses in speech fluency task-T2 ( r=0.46, P<0.05), whereas the left globus pallidus volume showed a negative correlation with speech fluency task-T1 ( r=-0.51, P<0.05) with the same measure. Conclusion:Lesions in the left subnuclei of the basal ganglia directly impair early-stage speech functions, including conceptual preparation and lexical selection, whereas right-side lesions exert less pronounced effects on linguistic performance compared to their left counterparts. Furthermore, the basal ganglia's involvement in higher-order linguistic processing may represent an indirect consequence of cognitive decline.

OBJECTIVE: To explore the expression and function of microRNA-144 (miR-144) in β-thalassemia (β-thal). METHODS: The expression of miR-144 during the differentiation of murine erythroleukemia (MEL) cells and mouse embryonic liver-derived erythroid precursor cells was analyzed by real-time fluorescence quantitative PCR (qRT-PCR); The expression levels of miR-144 in peripheral blood and day-14.5 embryonic hepatocytes of wild-type (WT) and β-thal mice, as well as the expression levels of miR-144 in peripheral blood of β-thal patients, was also measured by qRT-PCR. The proportion of Ter119 and CD71 double positive cells in peripheral blood of mild and severe β-thal mice was analyzed by flow cytometry, and the expression levels of miR-144 in the peripheral blood of mild and severe β-thal mice and patients were compared; Bone marrow nucleated erythrocytes from WT mice and β-thal mice were sorted and the expression levels of miR-144 potential target genes were analyzed by gene chip. RESULTS: The expression levels of miR-144 were gradually increased during the directed differentiation of mouse MEL cells and embryonic hepatocytes to the erythroid lineage (r _MEL=0.97, r _{embryonic hepatocytes}=0.86); Compared with WT mice, the expression levels of miR-144 in peripheral blood and 14.5-day embryonic hepatocytes of β-thal mice were significantly increased (P < 0.05); Compared with healthy controls, the patients with β-thal showed an increased expression levels of miR-144 in peripheral blood (P < 0.05). Compared with mice and humans with mild β-thal, the expression levels of miR-144 in peripheral blood of those with severe β-thal were significantly increased (P < 0.05). The expressions of potential target genes of miR-144 in nucleated erythroid cells of the β-thal mice were significantly reduced compared to the WT group. CONCLUSION The expression level of miR-144 gradually increases in erythroid development, and compared with mild β-thal patients, the expression level of miR-144 in the peripheral blood is higher in severe β-thal patients. MiR-144 is expected to be an auxiliary diagnostic indicator for β-thal in clinical practice.
MicroRNAs/metabolism* ; beta-Thalassemia/genetics* ; Animals ; Mice ; Humans ; Cell Differentiation ; Hepatocytes

OBJECTIVE: To investigate the application value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in etiological diagnosis of children with hematological malignancies complicated with pneumonia. METHODS: We retrospectively analyzed the clinical data of children with hematological malignancies who underwent BALF mNGS pathogenic detection due to pneumonia. All patients underwent mNGS detection of bronchoalveolar lavage fluid as well as traditional methods(including sputum culture, bronchoalveolar lavage fluid culture, blood culture, serological detection of pathogens, etc.). By analyzing the results of mNGS and traditional methods, we compared key indicators such as the positive rate, etiological distribution. RESULTS: A total of 26 children with hematological malignancies enrolled in the study, including 12 males and 14 females, with a median age of 4.9 (1.8-14.9) years, underwent bronchoalveolar lavage (BAL) 35 times. A total of 17 pathogenic microorganisms were detected in BALF mNGS, including 9 cases of bacterial infection, 10 cases of viral infection, 3 cases of fungal infection, 2 cases of mycoplasma infection and 8 cases of mixed infection, and the most commonly detected bacteria, viruses and fungi were streptococcus pneumoniae, cytomegalovirus and pneumocystis jirovecii, respectively. The positive rate of mNGS detection (91.43%) was significantly higher than that of traditional methods detection (20%, P <0.001). A total of 25 cases were adjusted according to BALF mNGS results. CONCLUSION The application of BALF mNGS technology can improve the detection rate of the pathogens in children with hematological malignancies complicated with pneumonia, initially revealed the pathogen spectrum of pulmonary infection in this group, and effectively guide clinical medication, improve treatment outcomes.
Humans ; Bronchoalveolar Lavage Fluid/microbiology* ; Hematologic Neoplasms/complications* ; Child ; Child, Preschool ; Infant ; Retrospective Studies ; Male ; Female ; Adolescent ; High-Throughput Nucleotide Sequencing ; Pneumonia/microbiology*

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

AIM:To investigate the effect of intrinsic specific transforming growth factor-β(TGF-β)signaling on regeneration and repair of myofibers in acute skeletal myositismice model induced by cardiotoxin(CTX).METHODS:One hundred and eighty-six wild C57BL/6 mice and one hundred and thirty-eight mice with conditional knockout of TGF-β receptor 2(TGF-βr2)in myofibers(SM TGF-βr2-/-mice)were selected.CTX injection to anterior tibial muscle(TA)in-duced acute myoinjury in mice.Some SM TGF-βr2-/-mice were given Smad signaling agonist SRI-011381(SRI)intramus-cular injection.All mice were mainly divided into the following groups:control group,SM TGF-βr2-/-group and SM TGF-βr2-/-+SRI group.Twenty-four mice were selected in each group.RT-qPCR and immunofluorescence staining were used to detect the relative mRNA level,protein expression of inflammatory cytokines and low-density lipoprotein receptor-related protein 1(LRP1),respectively,while the relative protein expression of myosin heavy chain 3(MHY3)and embryonic myosine heavy chain(eMHC)in damaged muscle was detected by Western blot and immunofluorescence staining.In vi-tro,after being extracted from neonatal mice,myogenic precursor cells(MPCs)were cultured in an pro-inflammatory mi-lieu and treated with SRI,recombinant mouse extracellular matrix protein 1(rmECM1)alone or in combination.Hereby,they were divided into the following seven groups:control-MPCs group,control-MPCs+LPS group,TGF-βr2-/--MPCs group,TGF-βr2-/--MPCs+LPS group,TGF-βr2-/--MPCs+LPS+SRI group,TGF-βr2-/--MPCs+LPS+rmECM1 group,and TGF-βr2-/--MPCs+LPS+SRI+rmECM1 group.Six mice were selected in each group.RT-qPCR and Western blot were used to detect the relative mRNA level,protein expression of major histocompatibility complex class I molecules(MHC-I/H-2Kb),major histocompatibility complex class II molecules(MHC-II/H2-Eα),Toll-like receptor 3(TLR3),and LRP1.And the relative protein expression of MoyD and myogenin in myotubes was detected by immunofluorescence staining.RE-SULTS:In vivo,compared with control group,SM TGF-βr2-/-group showed the significant upregulation of pro-inflamma-tory cytokines(P<0.05),and the opposite trend of anti-inflammatory cytokines,LRP1,MHY3,eMHC in the injured muscle(P<0.05),with delayed regeneration and repair of myofibers.In vitro,compared with control-MPCs+LPS group,LRP1,MoyD and myogenin significantly downregulated in TGF-βr2-/--MPCs+LPS group,but the downregulation trend was corrected after giving SRI treatment(P<0.05).In addition,compared with the TGF-βr2-/--MPCs+LPS group,the combi-nation of rmECM1 and SRI significantly upregulated the protein expression of MyoD and myogenin(P<0.05).CONCLU-SION:In a mouse model of acute skeletal myositis,intrinsic TGF-β signaling specifically in myofibers regulates local im-mune behavior.It promotes the expression of LRP1 in damaged muscle via Smad2/3 signaling,and LRP1 can then fully bind to ECM1,thereby facilitating muscle regeneration and repair,and improving the prognosis of acute skeletal myositis.