Engeletin alleviates depressive-like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway.

Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.

LncRNA CTBP1-AS inhibits TP63-mediated activation of S100A14 during prostate cancer progression.

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.

YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration.

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

Molecular and immunological features of TREM1 and its emergence as a prognostic indicator in glioma.

Triggering receptor expressed on myeloid cells 1 (TREM1), which belongs to the Ig-like superfamily expressed on myeloid cells, is reportedly involved in various diseases but has rarely been studied in glioma. In this study, the prognostic value and functional roles of TREM2 in glioma were analyzed. TERM1 was observed to be significantly upregulated in GBM compared to in other grade gliomas and was associated with poor prognosis. Increased TREM1 accompanied distinct mutation and amplification of driver oncogenes. Moreover, gene ontology and KEGG analyses showed that TREM1 might play a role in immunologic biological processes in glioma. TREM1 was also found to be tightly correlated with immune checkpoint molecules. xCell research revealed a link between TREM1 expression and multiple immune cell types, especially monocytes and macrophages. Single-cell analysis and immunofluorescence results showed that macrophages expressed TREM1. In vitro, inhibition of TREM1 signaling could result in a decrease in tumor-promoting effects of monocytes/TAMs. In summary, TREM1 may be a potential independent prognostic factor and immune target, which might provide new avenues to improve the efficacy of immunotherapy in glioma patients.

Ultrasonic-assisted activated carbon separation removing bacterial endotoxin from salvia miltiorrhizae injection.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Orthopedic mechanism analysis of growing rod distraction for early-onset scoliosis based on 3D morphological parameters.

Traditional growing rod (TGR) provides a corrective moment for deformed segments to straighten the spine, whose clinical efficacy has proven positive and growth-friendly. However, an insufficient understanding of orthopedic mechanisms can affect the development of clinical strategies. This research attempts to analyze the spine that has undergone four distraction operations: exploring the spinal orthopedic mechanism, including alignment, growth, and morphology. In this study, the spinal morphology curves were illustrated in three human planes to exhibit the changes in spinal alignment. The spinal growth characteristics were measured to discuss the unsynchronized and diminishing growth rate. The spinal deformations were evaluated to indicate asymmetric growth. As a result, the spinal alignment changes indicated the orthopedic process improved, but the re-unbalance occurred after multiple distractions. Then, unsynchronized growth existed in the superior and inferior segments, and the growth rate over every distraction diminished. Finally, asymmetric growth was indicated as the axial/circumferential growth ratio getting greater and the cuneate level approaching normal. Accordingly, a TGR is growth-friendly, but combining the osteotomy fusion of lumbar segments for severe early-onset scoliosis may be an excellent choice to solve the insufficient corrective stimulation. Regarding the distraction process, reshaping before the final fusion can fix the balance loss, and a prolonged distraction frequency fits the law of diminishing return. In conclusion, studying orthopedic mechanisms based on morphological measurement can guide clinical strategy optimization.

Mortality and years of life lost due to pancreatic cancer in China, its provinces, urban and rural areas from 2005 to 2020: results from the national mortality surveillance system.

BACKGROUND: Pancreatic cancer is a growing public health concern in China, and depicting it from different perspectives would provide a comprehensive understanding of its epidemiological characteristics. METHODS: Data from the National Mortality Surveillance System (NMSS) in China was used to estimate the number of deaths, years of life lost (YLL), age-standardized mortality rate (ASMR) and age-standardized YLL rate in China, its provinces and urban-rural areas from 2005 to 2020. Joinpoint regression analysis was employed to explore the temporal trends of ASMR and age-standardized YLL rate. Decomposition analysis was conducted to assess the contribution of population growth, population aging and cause-specific mortality rate to the increment of pancreatic cancer deaths. RESULTS: A total of 100,427 pancreatic cancer deaths and 2,166,355 pancreatic cancer related YLL were estimated in China in 2020. The overall ASMR significantly increased from 6.6/100 000 in 2005 to 7.4/100 000 in 2020, and was higher in men than that in women. Age-standardized YLL rate showed a similar trend. The mortality rates of pancreatic cancer were generally higher in northeast China than in southwest China. The highest ASMRs were found in Jilin, Zhejiang, Inner Mongolia and Anhui, and the lowest ones in Guangxi, Yunnan, Tibet, and Hainan. The disease burden due to pancreatic cancer presented a significant upward trend in rural areas and a downward trend in urban areas. CONCLUSIONS: The burden associated with pancreatic cancer had been increasing in China from 2005 to 2020. The escalating disease burden of pancreatic cancer in rural areas necessitates the implementation of effective control and prevention measures. Relevant provinces should pay greater attention to the prevailing of pancreatic cancer, particularly those exhibiting higher mortality rates.

African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction.

African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.

PPARγ activation suppresses chondrocyte ferroptosis through mitophagy in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a prevalent disease plaguing the elderly. Recently, chondrocyte ferroptosis has been demonstrated to promote the progression of OA. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important factor in maintaining cartilage health. However, the relationship between PPARγ and chondrocyte ferroptosis in OA and its mechanism is completely unclear. METHODS: We established a surgically induced knee OA rat model to investigate PPARγ and chondrocyte ferroptosis in OA. Rat knee specimens were collected for Safranin O/Fast Green staining and immunohistochemical staining after administered orally placebo or pioglitazone (PPARγ agonist) for 4 weeks. We used RSL3 to establish a chondrocyte ferroptosis model cultured in vitro to study the role of PPARγ activation toward ferroptosis, mitochondrial function, and PTEN-induced putative kinase 1 (Pink1)/Parkin-dependent mitophagy. GW9662 (PPARγ antagonist), Mdivi-1 (mitophagy inhibitor), and chloroquine (mitophagy inhibitor) were employed to investigate the mechanism of PPARγ-Pink1/Parkin-dependent mitophagy in the inhibition of ferroptosis. RESULTS: We found that PPARγ activation by pioglitazone attenuated not only OA but also inhibited the expression of the ferroptosis marker acyl-CoA synthetase long-chain family member 4 (ACSL4) at the same time in rats. Furthermore, in vivo and in vitro data indicated that PPARγ activation restored Pink1/Parkin-dependent mitophagy, improved mitochondrial function, inhibited chondrocyte ferroptosis, and delayed the progression of OA. CONCLUSIONS: The present study demonstrated that PPARγ activation attenuates OA by inhibiting chondrocyte ferroptosis, and this chondroprotective effect was achieved by promoting the Pink1/Parkin-dependent mitophagy pathway.

Microsurgical revascularization of a symptomatic proximal vertebral artery: pilot experiences from a single center.

Background: Vertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA. Methods: Twenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed. Results: Twelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner's syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8-62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported. Conclusion: Microsurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.

Mucinous cystadenocarcinoma of the ovary in a 14-year-old girl: a case report and literature review.

BACKGROUND: Ovarian epithelial tumors are common in adults, and their peak incidence of onset is over 40 years of age. In children, most ovarian tumors are germ cell-derived, whereas epithelial tumors are rare and mostly benign. CASE PRESENTATION: This report describes a case of a 14-year-old Chinese girl with ovarian mucinous cystadenocarcinoma. She was admitted with a small amount of bloody vaginal discharge during the past month. Magnetic resonance imaging of the abdomen and pelvis showed a large solid cystic mass lesion in the left ovary. Tumor marker levels were within normal limits ( CA-125: 22.3 U/mL, HE4: 28.5 pmol/L, HCG: < 1.20 mIU/ml, AFP: 3.3 ng/ml, CEA: 2.2 ng/ml, CA19-9: < 2.0 U/mL). Laparoscopic exploration revealed a large left ovarian tumor. The patient underwent left salpingo-oophorectomy, and showed no significant issues during follow-up, as well as no evidence of recurrence or metastasis. CONCLUSIONS: We report the first pediatric case of ovarian mucinous cystadenocarcinoma in China. Given the scarcity of reports addressing the clinical management of this condition, the present study provides a useful contribution to its further understanding in light of developing future treatment strategies.

Cancer stem cells promote lymph nodes metastasis of breast cancer by reprogramming tumor microenvironment.

Breast cancer progression and metastasis are governed by a complex interplay within the tumor immune microenvironment (TIME), involving numerous cell types. Lymph node metastasis (LNM) is a key prognostic marker associated with distant organ metastasis and reduced patient survival, but the mechanisms underlying its promotion by breast cancer stem cells (CSCs) remain unclear. Our study sought to unravel how CSCs reprogram TIME to facilitate LNM. Utilizing single-cell RNA sequencing, we profiled TIME in primary cancer and corresponding metastatic lymph node samples from patients at our institution. To verify the derived data, we cultured CSCs and performed validation assays employing flow cytometry and CyTOF. Our analysis revealed distinct differences in cellular infiltration patterns between tumor and LNM samples. Importantly, RAC2 and PTTG1 double-positive CSCs, which exhibit the highest stem-like attributes, were markedly enriched in metastatic lymph nodes. These CSCs are hypothesized to foster metastasis via activation of specific metastasis-related transcription factors and signaling pathways. Additionally, our data suggest that CSCs might modulate adaptive and innate immune cell evolution, thereby further contributing to metastasis. In summary, this study illuminates a critical role of CSCs in modifying TIME to facilitate LNM. The enrichment of highly stem-like CSCs in metastatic lymph nodes offers novel therapeutic targeting opportunities and deepens our understanding of breast cancer metastasis.

Gamma Knife surgery and deep brain stimulation of the centromedian nucleus for chronic pain: A systematic review.

Chronic pain has been a major problem in personal quality of life and social economy, causing psychological disorders in people and a larger amount of money loss in society. Some targets were adopted for chronic pain, but the efficacy of the CM nucleus for pain was still unclear. A systematic review was performed to summarize GK surgery and DBS of the CM nucleus for chronic pain. PubMed, Embase and Medline were searched to review all studies discussing GK surgery and DBS on the CM nucleus for chronic pain. Studies that were review, meet, conference, not English or not the therapy of pain were excluded. Demographic characteristics, surgery parameters and outcomes of pain relief were selected. In total, 101 patients across 12 studies were included. The median age of most patients ranged from 44.3 to 80 years when the duration of pain ranged from 5 months to 8 years. This review showed varied results of 30%-100% pain reduction across studies. The difference in the effect between GK surgery and DBS cannot be judged. Moreover, three retrospective articles related to GK surgery of the CM nucleus for trigeminal neuralgia presented an average pain relief rate of 34.6-82.5%. Four studies reported adverse effects in a small number of patients. GK surgery and DBS of the CM nucleus might be promising therapeutic approaches for chronic refractory pain. More rigorous studies and larger samples with longer follow-up periods are needed to support the effectiveness and safety.

A three-dimensional renal tumor anatomy and intrarenal relationship nephrometry (ADDD) for robot-assisted partial nephrectomy : 3D-CT based nephrometry for RAPN.

OBJECTIVE: To develop a 3D scoring system of tumor anatomy and intrarenal relationship for assessing surgical complexity and outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We prospectively enrolled patients with a renal tumor who had a 3D model and underwent RAPN between Mar 2019 and Mar 2022. The ADDD nephrometry consisted of the contact surface area between tumor and parenchyma (A), the depth of tumor invasion into the renal parenchyma (D1), the distance from tumor to the main intrarenal artery (D2), and to the collecting system (D3). The primary outcomes included perioperative complication rate and trifecta outcome (WIT ≤ 25 min, negative surgical margins, and no major complications). RESULTS: We enrolled a total of 301 patients. The mean tumor size was 2.93 ± 1.44 cm. There were 104 (34.6%) patients, 119 (39.5%) patients, and 78 (25.9%) patients in the low-, intermediate-, and high-risk groups, respectively. Each point increase in the ADDD score increased the risk of complications [hazard ratio (HR) 1.501]. A lower grade indicated a lower risk of failed trifecta (HR low group 15.103, intermediate group 9.258) and renal function damage (HR low risk 8.320, intermediate risk 3.165) compared to the high-risk group. The AUC of ADDD score and grade were 0.738 and 0.645 for predicting major complications, 0.766 and 0.714 for predicting trifecta outcome, and 0.746 and 0.730 for predicting postoperative renal function reservation. CONCLUSION: The 3D-ADDD scoring system shows the tumor anatomy and its intraparenchymal relationships and has better efficacy in predicting surgical outcomes of RAPN.

Effect of dietary antioxidants on the risk of prostate cancer. Systematic review and network meta-analysis.

Introduction: Objective: the purpose of this study was to assess the impact of 14 treatments including a total of 10 dietary antioxidants on the risk of prostate cancer. Material and methods: we searched PubMed, Embase, the Cochrane Library, and the Web of Science for only randomized controlled trials (RCTs) to investigate the effect of these 10 antioxidants on the risk of getting prostate cancer. Using the Cochrane Risk of Bias Assessment Tool, the methodological quality of the included studies was evaluated. Data extraction: studies were appraised by two investigators and data were extracted. Using a surface under cumulative ranking (SUCRA) probability, a Bayesian network meta-analysis was undertaken to evaluate the relative ranking of agents. Results: from the earliest accessible date through August 2022, RCTs were gathered. A total of 14 randomized controlled trials were included with a total sample size of 73,365 males. The results of the network meta-analysis showed that green tea catechins (GTCs) significantly reduced the risk of prostate cancer (SUCRA, 88.6 %) followed by vitamin D (SUCRA, 55.1 %), vitamin B6 (54.1 %), and folic acid was the lowest (22.0 %). Conclusion: based on the Ranking Plot of the Network, we can state that GTCs might have an impact on the prevention of prostate cancer compared to other dietary antioxidants, but we still need quality literature to further prove it.

Introducción: Objetivo: el propósito de este estudio fue evaluar el impacto de 14 tratamientos que incluyen un total de 10 antioxidantes dietéticos sobre el riesgo de cáncer de próstata. Material y métodos: buscamos en PubMed, Embase, la Biblioteca Cochrane y Web of Science solo ensayos controlados aleatorizados (ECA) para investigar el efecto de estos 10 antioxidantes sobre el riesgo de contraer cáncer de próstata. Se evaluó la calidad metodológica de los estudios incluidos mediante la herramienta Cochrane de evaluación del riesgo de sesgo. Extracción de datos: dos investigadores evaluaron los estudios y extrajeron los datos. Utilizando una probabilidad de clasificación acumulativa de superficie (SUCRA) se llevó a cabo un metanálisis de red bayesiano para evaluar la clasificación relativa de los agentes. Resultados: desde la primera fecha accesible hasta agosto de 2022, se recopilaron ECA. Se incluyeron 14 ensayos controlados aleatorizados con un tamaño de muestra total de 73.365 varones. Los resultados del metanálisis en red mostraron que las catequinas del té verde (GTC) redujeron significativamente el riesgo de cáncer de próstata (SUCRA, 88,6 %), seguidas de la vitamina D (SUCRA, 55,1 %), la vitamina B6 (54,1 %) y el ácido fólico fue el más bajo (22,0 %). Conclusión: según el diagrama de clasificación de la red, podemos afirmar que los GTC podrían tener un impacto en la prevención del cáncer de próstata en comparación con otros antioxidantes dietéticos, pero aún necesitamos literatura de calidad para demostrarlo.

Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer.

Background: Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. Methods: Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. Results: The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. Conclusions: These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats.

OBJECTIVES: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. METHODS: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1ß, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. RESULTS: After the treatment wound area rate, IL-1ß by ELISA, and IL-1ß, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. CONCLUSIONS: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

Risk factors and strategies for recovery quality, postoperative pain, and recurrent fractures between percutaneous kyphoplasty and percutaneous vertebroplasty in elderly patients with thoracolumbar compression fractures: a retrospective comparative cohort study.

Background: With the increase of clinical cases and the improvement of operation, we found that recurrent fracture of the adjacent vertebral body is a common long-term complication of percutaneous kyphoplasty (PKP). However, the mechanism of re-fracture of adjacent vertebrae after PKP has not been unified. Therefore, through retrospective study, this paper discussed the risk factors and countermeasures affecting the quality of rehabilitation, postoperative pain and recurrent fracture in elderly PKP patients. Methods: From December 2019 to May 2021, 313 patients with osteoporotic spinal fractures were analyzed retrospectively. Cases were allocated to percutaneous vertebroplasty (PVP; n=130) and PKP (n=183) groups according to the modes of operation. Visual analogue scale (VAS), Cobb angle, and Oswestry disability index (ODI) were evaluated. Based on the occurrence of new fractures, the PKP cohort (n=15) and control cohort (n=32) were classified. Questionnaires analyzed the postoperative re-fractures of people with different characteristics, and the influencing factors of postoperative re-fracture were measured by multivariate logistic regression analysis. Results: The postoperative VAS scores were significantly lower in the PKP group. The ODI scores in the PKP group were considerably lower than those in the PVP group after surgery. Univariate analysis indicated that age, number of injured vertebrae, history of complicated fracture, number of operative vertebrae, and bone mineral density (BMD) were remarkably correlated with recurrent fracture after PKP. Logistic regression analysis indicated that age, operative vertebral body, BMD, and the number of injured vertebrae were independent risk factors for recurrent fracture after PKP. BMI, BMD, low back soft tissue injury, postoperative vertebral height recovery rate, sagittal Cobb angle improvement rate, total diffusion coefficient of bone cement, short-term complications, non-union, and recurrent fracture were the main risk factors of residual low back pain after PKP. Conclusions: The clinical efficacy of PKP in elderly patients with thoracolumbar vertebral compression fracture is superior to that of PVP. Clinical attention should be paid to identifying high-risk factors for complications after PKP, and preventive measures should be implemented to help reduce the occurrence of recurrent fractures and postoperative residual pain.

Gamma Knife Radiosurgery for Cushing's Disease: Evaluation of Biological Effective Dose from a Single-Center Experience.

Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing's disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS.

Reconstructive endovascular treatment for basilar artery trunk aneurysms: complications and clinical and angiography outcomes.

BACKGROUND: Basilar artery trunk aneurysms (BTAs) are rare intracranial aneurysms. We aim to investigate the procedural complications and clinical and angiographic outcomes of BTAs treated with reconstructive endovascular treatment (EVT). METHODS: We retrospectively reviewed the data of 111 patients with BTAs who underwent reconstructive EVT during 2013-2022. The factors associated with procedural complications and clinical and angiographic outcomes were analyzed. RESULTS: The study included 81 men and 30 women (median age 60 years). Overall, 26 (23.4%) cases presented with subarachnoid hemorrhage and 85 (76.6%) presented with unruptured aneurysms. Periprocedural ischemic and hemorrhagic complications occurred in 29 (26.1%) and 4 (3.6%) cases, respectively. The rate of favorable clinical outcomes was 83.8% (92/111) and the mortality rate was 14.4% (16/111). Angiographic follow-up data were available for 77/95 (81.1%) survivors; 57 (74.0%) and 20 (26%) aneurysms exhibited complete and incomplete obliteration, respectively. Old age, high Hunt and Hess grades (IV-V), hemorrhagic complications, and increased aneurysm size were independent risk factors for unfavorable clinical outcomes (p<0.05). Increased aneurysm size and incomplete aneurysm occlusion on immediate angiography were independent risk factors for incomplete occlusion during follow-up (p<0.05). CONCLUSION: Reconstructive EVTs are a feasible and effective treatment for BTAs but are associated with a high risk of ischemic and hemorrhagic complications and a high mortality rate. Larger aneurysms may predict unfavorable clinical outcomes and aneurysm recurrence during follow-up. Hemorrhagic complications may predict unfavorable clinical outcomes, whereas immediate complete aneurysm occlusion may predict total occlusion during follow-up.