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BACKGROUND: Percutaneous Endoscopic Lumbar Discectomy (PELD) has emerged as routine treatment for lumbar disc herniation (LDH) due to its minimal invasiveness and quick recovery. However, PELD demands high precision from the surgeon, as the risk of intraoperative complications is substantial, including potential damage to the nerve root and dura, and a higher likelihood of recurrence post-surgery. Thus, preoperative planning utilizing CT and MRI imaging is essential. METHODS: In this study, the clinical data of 140 patients treated with PELD for LDH from January 2021 to December 2023 were retrospectively analyzed. Patients were categorized into two groups based on whether CT and MRI registration (CMR) was employed for surgical planning: a CMR group (n=68) and a control group (n=72). Data collected included surgery time, hospital stay duration, and scores from the Visual Analog Scale (VAS) for low back and leg pain, as well as the Japanese Orthopaedic Association Lumbar Spine Score (JOA). Differences between the two groups were assessed using the Student's t-test. RESULTS: No significant difference was found in hospital stay length between the groups (P=0.277). Surgery time was significantly shorter in the CMR group (P<0.001). Prior to surgery, no significant differences in VAS scores for leg and low back pain were observed between the groups (P=0.341 and P=0.131, respectively); however, at 2 months postoperatively, both scores were significantly lower in the CMR group (P<0.001 and P=0.002, respectively). Similarly, no difference in preoperative JOA scores was noted (P=0.750), but at 2 months postoperative, the CMR group exhibited significantly higher scores (P<0.001). CONCLUSION: Compared with the traditional PELD, the preoperative use of CMR has shown to reduce surgery time, alleviate leg and low back pain, and increase the lumbar JOA score at 2 months after surgery, underscoring its efficacy in enhancing surgical outcomes.
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The profiling of the tumor immune microenvironment (TIME) is critical for guiding immunotherapy strategies. However, how the composition of the immune landscape affects the tumor progression of gastric cancer (GC) is ill-defined. Here, we used mass cytometry to perform simultaneous in-depth immune profiling of the tumor, adjacent tissues, and blood cells from GC patients and revealed a unique GC tumor-immune signature, where CD8+ T cells were present at a lower frequency in tumor tissues compared to adjacent tissues, whereas regulatory T cells and tumor-associated macrophages (TAMs) were significantly increased, indicating strong suppressive TIME in GC. Incorporated with oncogenic genomic traits, we found that the unique immunophenotype was interactively shaped by a specific GC gene signature across tumor progression. Earlier-stage GC lesions with IFN signaling enrichment harbored significantly altered T-cell compartments while advanced GC featured by metabolism signaling activation was accumulated by TAMs. Interestingly, PD-1 expression on CD8+ T cells was relatively higher in earlier-stage GC patients, indicating that these patients may derive more benefits from PD-1 inhibitors. The dynamic properties of diverse immune cell types revealed by our study provide new dimensions to the immune landscape of GC and facilitate the development of novel immunotherapy strategies for GC patients.
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Neoplasias Gástricas , Linfocitos T CD8-positivos , Humanos , Inmunofenotipificación , Neoplasias Gástricas/patología , Linfocitos T Reguladores , Microambiente TumoralRESUMEN
INTRODUCTION: The characteristics of the tumor immune microenvironment (TIME) are closely related to immunotherapy. Breast cancer can benefit from immunotherapy, and its TIME is still unclear. METHODS: We utilized mass cytometry to explore the immune cell heterogeneity in breast cancer. Double-negative T cells (DNTs) from healthy volunteers (HBs) were enriched in vitro. Flow cytometry was used to detect the cell surface receptors of cancer cells and DNT cells. The correlation between immune checkpoints and the abundance of immune cells or prognosis of breast cancer was analyzed by the TCGA database. The messenger RNA (mRNA) expression of functional genes was performed by quantitative real-time PCR. RESULTS: We found that the frequencies of Granzyme B (GZMB)+ CD8+ T and GZMB+ DNT cells in cancer tissues (CA) of breast cancer were lower than those in blood samples of patients (PB), and the frequencies of programmed cell death protein 1 (PD1)+ CD8+ T and PD1+ DNT cells in CA were higher than those in PB. DNTs from HBs had a cytotoxic effect on MDA-MB-231. LAG3Ab could upregulate the mRNA expression of interferon gamma and perforin by increasing T-BET transcription to enhance the cytotoxicity of DNT cells in vitro. CONCLUSION: Our study revealed the suppressive status of TIME in breast cancer and supported DNT cells had the potential to be applied as a novel adoptive cell therapy for TNBC either alone or combined with LAG3Ab.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Inmunoterapia Adoptiva , ARN Mensajero , Linfocitos T , Microambiente TumoralRESUMEN
BACKGROUND: Fat embolism syndrome (FES) is a rare complication caused by the presence of fat particles in the microcirculation, which usually occurs within 12-72 h after trauma. At present, there have been few cases of fat embolism presenting within 3 h after trauma. Here, we report a case of femoral fracture complicated with an acute fat embolism caused by a car accident. CASE SUMMARY: A 29-year-old woman with pain, swelling and limited movement of her left lower limb after a car accident was taken by ambulance to our hospital. X-ray examination showed fracture of the middle and lower part of the left femur and fracture of the base of the left fifth metatarsal bone. She was hospitalized and admitted to the orthopedic ward. After the attending doctor performed tibial tubercle bone traction, the patient became confused, followed by respiratory distress. Finally, she was transferred to the intensive care unit. After nearly a month of treatment in the intensive care unit, the patient's cognitive function gradually recovered over 6 mo. CONCLUSION: For patients with early traumatic fractures, young emergency physicians and orthopedics should be aware of the possibility of FES.
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The combination of immune-checkpoint blockade (ICB) and lenvatinib has demonstrated robust clinical effects that are superior to those of monotherapies, but the synergistic anti-tumor mechanisms remain unclear. Exploring the synergistic molecular mechanisms and early identifying potential application have key importance for clinical therapeutics. We firstly systematically reviewed published data of ICB in combination with lenvatinib for the treatment of cancer by meta-analysis. A subsequent bioinformatics analysis explored the mechanism of combined ICB and lenvatinib therapy in 33 cancer types. Transcriptomic analysis was conducted by RNA-seq, and genomic analysis was performed on gene mutations and copy-number alteration data. Tumor-related pathways and tumor immune micro-environment (TIME) were also investigated. The meta-analysis showed a 38.0% objective response rate (ORR) and 79% disease control rate (DCR) for ICB combined with lenvatinib. Multi-omics analysis revealed that ICB and lenvatinib target genes were highly expressed and showed driving alterations in six specific malignancies. Pathway-enrichment analysis found target genes were implicated in tumor development, angiogenesis, and immunoregulatory associated pathways. This study verified the potential synergistic mechanisms of ICB combined with lenvatinib at transcriptomics, genomics, protein, and cellular levels and recognized nine tumor types had ≥ 2 positive treatment-related molecular characteristics, which might benefit particularly from this combined strategy. The findings would help to provide clinical insights and theoretical basis for optimizing of targeted therapy-immunotherapy combinations, and for guiding individualized precision-medicine approaches for cancer treatment.
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INTRODUCTION: Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors are proved to be promising and are applied for the treatment of a variety of solid tumors. This retrospective study evaluated the efficacy of PD-1/PD-L1 inhibitors in patients with advanced solid tumors and explore the effect of clinical characteristics on it. MATERIALS AND METHODS: From October 2017 to April 2020, a total of 90 patients from Capital Medical University Affiliated Beijing Friendship Hospital were enrolled. RESULTS: At a median follow-up of 10.55 months, objective response was observed in 23 patients and the objective response rate was 25.6%. The median progression-free survival (PFS) was 5.5 months (95% confidence interval [CI], 3.69-7.37). The 6m-PFS was 45.8% and 12m-PFS was 25.1%. The median overall survival (OS) was 16.9 months (95% CI, not reached [NR]-NR). The 12m-OS was 58.1% and 18m-OS was 48.1%. CONCLUSION: The efficacy of PD-1/PD-L1 inhibitors in the treatment of advanced solid tumors was comparable to previous studies. ECOG performance status, smoking status, liver metastasis, neutrophil-to-lymphocyte ratio were independently correlated with PFS while liver metastasis and lactate dehydrogenase level were independently correlated with OS.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Estudios RetrospectivosRESUMEN
BACKGROUND This study aimed to evaluate Sanders type 2 calcaneal fractures in 197 patients from a single center using the 3D (three-dimensional) CT (computed tomography) mapping method. MATERIAL AND METHODS A consecutive series of 197 Sanders type 2 joint depression calcaneal fractures was used. The segment and split functions were used to create each calcaneal fragment using Mimics Research 20.0 software. The fracture fragments were reduced in 3-matic Research 12.0 software. In the E-3D Medical 18.01 software, after superimposing the fractured calcaneus entity with the calcaneus template, we drew the fracture line on the template. Finally, the heatmap was obtained by fracture statistical analysis function. Simultaneously, the distribution of the fracture lines in the anterior part of the calcaneus (APC) and middle talar joint was recorded. RESULTS There were 109 cases of Sanders type 2A, 46 cases of Sanders type 2B, and 42 cases of Sanders type 2C. Based on the data, we drew the characteristic fracture map of type 2A 2B and 2C. This study found that the most common types of Sanders type 2A in APC and middle talar articular surface are type AC and type AD. In Sanders type 2B, the most common type is type AC, and in Sanders type 2C it is type ACD. CONCLUSIONS The findings from this study showed that 3D CT imaging and reconstruction of the calcaneus was a useful diagnostic method to evaluate and classify joint depression calcaneal fractures. The calcaneal fracture map can be used to guide surgical planning and optimize the design of internal fixation.
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Calcáneo/diagnóstico por imagen , Calcáneo/lesiones , Fracturas Óseas/diagnóstico por imagen , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: This study aimed to evaluate tongue-type calcaneal fractures using three-dimensional (3D) computed tomography (CT) mapping method. METHODS: A consecutive series of 136 tongue-type calcaneal fractures was used. CT data were used to reconstruct and reposition the 3D calcaneus body. E-3D Medical 18.01 software was used to superimpose the fractured calcaneal entity on the template, and the fracture line was drawn on the template. Finally, the heatmap was obtained using the fracture statistical analysis function. At the same time, the distribution of fracture lines in the anterior part of the calcaneus (APC) was recorded. Cases were divided into the following 3 subtypes according to the distribution of the tongue-type fracture lines of the calcaneal body: medial-lateral (Group A), upper-lateral (Group B), and upper-lateral-medial (Group C). RESULTS: There were 68 cases in Group A, 48 cases in Group B, and 20 cases in Group C. Based on subtype, the characteristic fracture map of Groups A, B and C was constructed. The APC was evenly divided into zones A, B, and C from lateral to medial. In Group A, the most common types involve APC were Type AC (24, 35.3%) and Type A (11, 16.2%). In Group B, the most common types were Type AC (20, 41.7%), Type AB (8, 16.7%) and Type C (8, 16.7%). In Group C, the most common types were Type AC (8, 40.0%) and Type A (5, 25.0%). CONCLUSIONS: This study investigates the distribution characteristics of fracture lines in subgroups of tongue-type calcaneal fractures for the first time. The results can help doctors improve their understanding of tongue-type calcaneal fractures, optimize internal fixation design, and provide a standard model for biomechanical experiments.
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BACKGROUND: PD-1/PD-L1 inhibitors have made unprecedented progress in the treatment of cancer. METHODS: A systemic search was conducted for randomized controlled trials that compared PD-1/PD-L1 inhibitor monotherapy or combination therapy with nonimmunotherapy. Hazard ratios (HRs) of overall survival (OS) according to the sex, age, ECOG PS, smoking status, liver metastasis, PD-L1 expression, EGFR, and KRAS status of patients were analyzed. RESULTS: Totally, 13 studies with monotherapy and 5 with combination regimens were included, and the pooled HRs of OS were 0.74 (P < 0.001) and 0.64 (P < 0.001), respectively. EGFR wild-type patients could benefit from immunotherapy monotherapy (HR, 0.77; P < 0.001) while those of the mutant type had no survival benefit (HR, 1.11; P = 0.54), and the difference was statistically significant (interaction, P = 0.005). KRAS wild-type patients had no survival benefit from monotherapy (HR, 0.89; P = 0.49). For combination therapy, both male and female derived benefits but female had a significantly reduced risk of death (HR, 0.45; P < 0.001) compared with male (HR, 0.73; P < 0.001; interaction, P = 0.004). Nonsmokers derived more survival benefits from combination therapy (HR, 0.29; P < 0.001) than smokers (HR, 0.63; P = 0.001; interaction, P = 0.02). No significant difference was found between age, ECOG PS, liver metastasis, PD-L1 expression, and OS of both PD-1/PD-L1 inhibitor monotherapy and combination therapy. CONCLUSIONS: Both PD-1/PD-L1 inhibitor monotherapy and combination therapy significantly prolonged the OS of patients with advanced malignant tumors. EGFR status for monotherapy and sex and smoking status for combination therapy were important predictors of survival benefits.
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Neoplasias/mortalidad , Neoplasias/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
Immune surveillance cells in the tumor microenvironment play an important role in inhibiting tumorigenesis and metastasis, but their anti-tumoral effects are impaired. The anti-tumoral effects of innate immune cells and adaptive immune cells in the immune microenvironment of gastric cancer are also impaired. Their degree of functional impairment is closely related to the prognosis of gastric cancer. Multiple factors inhibit the anti-tumoral effects of immune surveillance cells, such as decreased numbers of immune surveillance cells, reduced activating receptors, decreased secretion of pro-inflammatory cytokines, increased apoptosis, elevated expression of coinhibitory molecules on cancer cells or immunosuppressive cells, increased secretion of inhibitory cytokines, impaired antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by antigen-presenting cells (APCs) and pro-tumoral polarization of cells with functional plasticity. These factors can potentially combine to suppress the immune surveillance cells' functions. However, there are conflicting conclusions on the effects of immune surveillance cells on gastric cancer cells. These contradictions are partly due to the heterogeneity of the tumor microenvironment.
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Neoplasias Gástricas/inmunología , Microambiente Tumoral/inmunología , Inmunidad Adaptativa , Animales , Humanos , Inmunidad Innata , Vigilancia InmunológicaRESUMEN
Diabetes is known to exacerbate cerebral ischemia/reperfusion (I/R) injury. Here, we investigated the effects of Clostridium butyricum on cerebral I/R injury in the diabetic mice subjected to 30min of bilateral common carotid arteries occlusion (BCCAO). The cognitive impairment, the blood glucose level, neuronal injury, apoptosis, and expressions of Akt, phospho-Akt (p-Akt), and caspase-3 level were assessed. Meanwhile, the changes of gut microbiota in composition and diversity in the colonic feces were evaluated. Our results showed that diabetic mice subjected to BCCAO exhibited worsened cognitive impairment, cell damage and apoptosis. These were all attenuated by C. butyricum. Moreover, C. butyricum reversed cerebral I/R induced decreases in p-Akt expression and increases in caspase-3 expression, leading to inhibiting neuronal apoptosis. C. butyricum partly restored cerebral I/R induced decreases of fecal microbiota diversity, changes of fecal microbiota composition. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain probiotics might prove to be useful therapeutic adjuncts in cerebral I/R injury with diabetes.
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Isquemia Encefálica/microbiología , Isquemia Encefálica/prevención & control , Clostridium butyricum/fisiología , Complicaciones de la Diabetes , Microbioma Gastrointestinal , Animales , Apoptosis , Glucemia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicología , Complicaciones de la Diabetes/microbiología , Diabetes Mellitus Experimental/complicaciones , Hipocampo/metabolismo , Hipocampo/microbiología , Hipocampo/patología , Masculino , Aprendizaje por Laberinto , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión/metabolismo , Daño por Reperfusión/microbiología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/psicologíaRESUMEN
Probiotics participate actively in the neuropsychiatric disorders. However, their roles on ischemic stroke remain unclear. This study aims to determine whether Clostridium butyricum (C. butyricum) could attenuate cerebral ischemia/reperfusion (I/R) injury and its possible mechanisms. Male ICR mice were intragastrically pretreated with C. butyricum for 2 successive weeks, and then subjected to cerebral I/R injury induced by the bilateral common carotid artery occlusion (BCCAO) for 20min. After 24h of the reperfusion, neurological deficit scores were evaluated. Histopathological changes of the hippocampus neurons were observed using Hematoxylin and eosin (H&E) and TUNEL staining. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the brain were detected. The expression of Caspase-3, Bax and Bcl-2 were investigated by Western blot and immunohistochemistry analysis. The butyrate contents in the brain were determined. Our results showed that cerebral I/R injury led to neurological deficit, increased levels of Caspase-3 and Bax and decreased Bcl-2/Bax ratio. C. butyricum significantly improved neurological deficit, relieved histopathologic change, decreased MDA contents and increased SOD activities in the I/R injury mice. After C. butyricum pretreatment, the expression of Caspase-3 and Bax were significantly decreased, the Bcl-2/Bax ratio was significantly increased, and butyrate contents in the brain were significantly increased. These findings suggested that C. butyricum is able to exert neuroprotective effects against I/R injury mice through anti-oxidant and anti-apoptotic mechanisms, and reversing decrease of butyrate contents in the brain might be involved in its neuroprotection.
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Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Clostridium butyricum , Estrés Oxidativo , Probióticos/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/etiología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Arteria Carótida Común/patología , Estenosis Carotídea/complicaciones , Caspasa 3/metabolismo , Masculino , Ratones Endogámicos ICR , Neuronas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.
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Butiratos/metabolismo , Clostridium butyricum , Demencia Vascular/terapia , Fármacos Neuroprotectores/farmacología , Probióticos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/microbiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Arterias Carótidas/patología , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos ICR , Microscopía Electrónica , Fosfatidilinositol 3-Quinasas/metabolismo , FosforilaciónRESUMEN
Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1ß, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.