Identification and clinical validation of the role of anoikis-related genes in diabetic foot.

This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.

SLC25A32 promotes malignant progression of glioblastoma by activating PI3K-AKT signaling pathway.

BACKGROUND: Solute carrier family 25 member 32 (SLC25A32) is an important member of SLC25A family and plays a role in folate transport metabolism. However, the mechanism and function of SLC25A32 in the progression of human glioblastoma (GBM) remain unclear. METHODS: In this study, folate related gene analysis was performed to explore gene expression profiles in low-grade glioma (LGG) and GBM. Western blotting, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were used to confirm the expression levels of SLC25A32 in GBM tissues and cell lines. CCK-8 assays, colony formation assays, and Edu assays were performed to assess the role of SLC25A32 on proliferation in GBM in vitro. A 3D sphere invasion assay and an ex vivo co-culture invasion model were performed to assess the effects of SLC25A32 on invasion in GBM. RESULTS: Elevated expression of SLC25A32 was observed in GBM, and high SLC25A32 expression was associated with a high glioma grade and poorer prognosis. Immunohistochemistry performed with anti-SLC25A32 on samples from an independent cohort of patients confirmed these results. Knockdown of SLC25A32 inhibited the proliferation and invasion of GBM cells, but overexpression of SLC25A32 significantly promoted cell growth and invasion. These effects were mainly due to the activation of the PI3K-AKT-mTOR signaling pathway. CONCLUSION: Our study demonstrated that SLC25A32 plays a significant role in promoting the malignant phenotype of GBM. Therefore, SLC25A32 can be used as an independent prognostic factor in patients with GBM, providing a new target for the comprehensive treatment of GBM.

Fully neuroendoscopic resection of cerebellopontine angle tumors through a retrosigmoid approach: a retrospective single-center study.

The objective of this study is to preliminarily investigate the surgical safety, efficacy, techniques, and clinical value of fully neuroendoscopic surgery for the resection of cerebellopontine angle (CPA) tumors via a retrosigmoid approach. The clinical data of 47 cerebellopontine angle area (CPA) tumors that were treated by full neuroendoscopic surgery from June 2014 to June 2023 were retrospectively analyzed. The efficacy and advantages of the surgical techniques were evaluated based on indicators such as duration of the surgery, neuroendoscopic techniques, intraoperative integrity of nerves and blood vessels, extent of tumor resection, outcomes or postoperative symptoms, and incidence of complications. The 47 cases of cerebellopontine angle tumors include 34 cases of epidermoid cysts, 7 cases of vestibular schwannomas, and 6 cases of meningiomas. All patients underwent fully neuroendoscopic surgery. Twenty tumors were removed using the one-surgeon two-hands technique, and 27 tumors were removed using the two-surgeons four-hands technique. The anatomical integrity of the affected cranial nerves was preserved in all 47 cases. None of the patients suffered a postoperative hemorrhage, cerebrospinal fluid leak, and aseptic or septic meningitis, or died. The rate of total tumor resection was 72.3% (34/47), and the symptom improvement rate was 89.4% (42/47). All patients were followed up for 2 to 12 months, and none died nor showed any signs of tumor recurrence. By analyzing 47 fully neuroendoscopic resections of CPA tumors using the posterior sigmoid sinus approach in our center, we believe that such method allows complete, safe, and effective resection of CPA tumors and is thereby worthy of clinical promotion.

[Sperm DNA damage is not related to seminal leukocyte subsets in infertile males with asymptomatic genital tract infection].

OBJECTIVE: To study the correlation of leukocyte subsets with sperm DNA damage in the semen of infertile men with asymptomatic genital tract infection (AGTI). METHODS: This study included 111 infertile males with AGTI. After routine semen analysis, we determined the concentration of CD45+ leukocytes in the semen by immunocytochemistry, measured the concentrations of CD14+ cells of the mononuclear / macrophagic system and activated macrophages and HLA-DR+ cells in the semen by flow cytometry, and examined the sperm DNA fragmentation index (DFI) and the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) by TUNEL assay. Then we analyzed the correlation of seminal leukocyte subsets with sperm DNA damage and routine semen parameters. RESULTS: The concentration of CD45+ leukocytes was correlated significantly with those of CD14+ and HLA-DR+ cells in the semen (P <0.01), but not that of leukocyte subsets with routine semen parameters, sperm DFI, or the percentage of 8-OHdG-positive cells. The percentage of 8-OHdG-positive sperm was correlated positively with the sperm DFI (r = 0.48, P<0.01) but negatively with sperm concentration (r = －0.44, P <0.01). After adjusted for age, abstinence time and cigarette smoking, the percentage of 8-OHdG-positive sperm was correlated independently with sperm concentration (ß = －0.25, P = 0.008) and DFI (ß = 0.23, P = 0.05). CONCLUSIONS: Sperm DNA damage is associated with poor semen quality but not with seminal leukocyte subsets in infertile males with asymptomatic genital tract infection.

Pramipexole has a neuroprotective effect in spinal cord injury and upregulates D2 receptor expression in the injured spinal cord tissue in rats.

Spinal cord injury (SCI) has emerged as a prevalent condition with limited effective treatment options. The neuroprotective role of pramipexole (PPX) in inhibiting nerve cell apoptosis in central nervous system injuries is well established. Therefore, we investigated the effects of PPX in SCI. Adult Sprague-Dawley rats were divided into four groups (sham, SCI, PPX-0.25, and PPX-2.0 groups) according to the PPX therapy (n = 24). Then, SCI was induced using the modified Allen method, and PPX was intravenously administered into the tail at dosages of 0.25 or 2.0 mg/kg following the injury. Motor function was evaluated using the Rivlin-modified inclined plate apparatus and the Basso Beattie Bresnahan (BBB) workout scale. Western blotting assay was used to measure protein expression levels of DRD2, NeuN, Bax/Bcl-2, and caspase-3. Furthermore, immunohistochemistry assessed the effect of PPX on the quantity of NeuN-positive cells in the spinal cord tissue after SCI. Our findings revealed that the BBB and slanting board test scores of the PPX-treated model groups were considerably higher for the SCI group and significantly lower for the sham operation group (P < 0.001). Moreover, the PPX-2.0 group exhibited significantly higher NeuN expression levels than the SCI group (P < 0.01). Our findings indicate that PPX exerts a neuroprotective effect in secondary neuronal injury following SCI, facilitating the recovery of hind limb function by downregulating Bax/Bcl-2, caspase-3, and IL-1ß.

Temperature Field and Stress Analysis of the Heavy-Concrete Transfer-Purge Chamber of the Nuclear Power Plant.

A transfer-purge chamber (TPC) is a double-steel-plate, heavy-concrete, curved-surface composite structure composed of steel plates, heavy concrete, and shear connectors. It is an important facility in the external refueling system of a nuclear power plant (NPP), providing a safe and reliable biological shielding space for reactor refueling operations. Temperature load is one of the most important factors that must be considered in the design of NPP structures. The temperature loads experienced by the TPC during its life cycle include those encountered in both normal and abnormal operation, which are distinct. In this study, we investigated the steady state and transient-state temperature fields and stresses of a TPC structure under normal operation and after 48 h of abnormal operation, respectively, which were calculated using Abaqus finite element software and the directly coupled method. During normal operation, the temperature field of the structure shows relatively uniform changes, and the temperature gradient of the internal concrete in the direction of its thickness has a constant value of 0.245 °C/cm. At the junction between the transfer and purge sub-chambers of the TPC, under the influence of wall curvature and deformation constraints, the maximum tensile strain of heavy concrete is 8.84 × 10-3, the maximum compressive strain is 2.04 × 10-3, the peak stress of the steel plate is 98.305 MPa, and the peak stress of the stud is 306.725 MPa. After 48 h of abnormal operation, the temperatures of the inner surface of the heavy concrete of the wall, the inner steel plate of the wall, the outer surface of the heavy concrete of the wall, and the inner steel plate of the wall increased by 8.12, 8.11, 0.31, and 0.30 °C, respectively. The tensile strain of the heavy concrete of the wall increased significantly by 52.64%, and the compressive strain of the concrete increased by 67.33%, whereas the stresses of the studs and steel plates increased by only 1.57% and 6.79%, respectively. These results show that the change in the temperature field greatly influences the stress and strain on the TPC structure. As measures for mitigating the development of this unfavorable situation of temperature stress concentration, the temperature operating range should be rationally controlled or the junction structure between the transfer and purge sub-chambers of the TPC optimized accordingly. The results of our study can provide basic data for a dynamic analysis of the TPC under conditions of combined earthquake and temperature loads.

Physiological Mechanism of Waterlogging Stress on Yield of Waxy Maize at the Jointing Stage.

In the main agricultural area for waxy maize production in China, waterlogging occurs frequently during the waxy maize jointing stage, and this causes significant yield reduction. It is very important to understand the physiological mechanism of waterlogging stress in waxy maize during the jointing stage to develop strategies against waterlogging stress. Therefore, this study set waterlogging treatments in the field for 0, 2, 4, 6, 8, and 10 days during the waxy maize jointing stage, and were labelled CK, WS2, WS4, WS6, WS8 and WS10, respectively. By analyzing the effect of waterlogging on the source, sink, and transport of photoassimilates, the physiological mechanism of waterlogging stress in the jointing stage was clarified. The results show that PEPC and POD activities and Pro content decreased significantly under WS2 compared to CK. Except for these three indicators, the Pn, GS, leaf area, kernel number, yield, and puncture strength of stems were significantly decreased under the WS4. Under the WS6, the content of MDA began to increase significantly, while almost all other physiological indices decreased significantly. Moreover, the structure of stem epidermal cells and the vascular bundle were deformed after 6 days of waterlogging. Therefore, the threshold value of waterlogging stress occured at 4 to 6 days in the jointing stage of waxy maize. Moreover, waterlogging stress at the jointing stage mainly reduces the yield by reducing the number of kernels; specifically, the kernel number decreased by 6.7-15.5% in 4-10 days of waterlogging, resulting in a decrease of 9.9-20.2% in the final yield. Thus, we have shown that waterlogging stress at the jointing stage results in the decrease of potential waxy maize kernel numbers and yield when the synthesis of sources was limited and the transport of photoassimilates was restricted.

Shaking Table Test of a Transfer-Purge Chamber in Nuclear Island Structure.

The transfer-purge chamber is an operation room for nuclear fuel transport and purging in a nuclear power plant, which has a demand for structural reliability and radiation protection. The transfer-purge chamber has features such as large curvature, heavy concrete, long overhang, and irregular cross-sections, and it is constructed of double steel plates reinforced concrete (SC) structure. This study performed shaking table tests for a 1:4.5 scale model of the transfer-purge chamber. Three sets of ground motions were input in the scale model in the horizontal and vertical directions to study its structural reliability and seismic performance. Acceleration response and strain response of the structure were analyzed to evaluate the dynamic characteristics of the transfer-purge chamber under the ground motion. The results show that the transfer-purge chamber has great stiffness and short periods. The periods slightly increase with the rise of intensity of seismic ground motions. Under the excitation of ground motions, the dynamic response of the transfer-purge chamber is slight. No obvious deformation or damage occurred on the transfer-purge chamber, and cracking in concrete or buckling on steel plate did not appear. The transfer-purge chamber has excellent seismic performance, and it is sufficiently safe and reliable from a structural perspective.

Ecological risk assessment and environment carrying capacity of soil pesticide residues in vegetable ecosystem in the Three Gorges Reservoir Area.

Soil contamination by pesticide residues has become an increasing concern of ecological protection. However, the soil environmental carrying capacity (SECC) of pesticide residues in agricultural ecosystems was limited studied. Based on the concept of ecological risk assessment, a modified system on the environment carrying capacity was proposed for estimate SECC of pesticide residues in agricultural soils. Subsequently, the assessment on ecological risk and SECC of soil pesticide residues in vegetable ecosystem were performed in the Three Gorges Reservoir Area (TGRA). In 201 topsoil samples, 62.1% of the pesticide compounds were detected over limit of quantitation, and exhibit a high proportion of multiple pesticide contamination. Pyrethroid insecticides and herbicide glyphosate showed most frequent occurrence and high levels. The SECC of the TGRA varies with the limit standard, annual cumulative amount and risk quotient of each pesticide contaminant in soils. Except that fenpropathrin has exceeded SECC, chlorfenapyr, ß-cyfluthrin and glyphosate posed the greatest threat to SECC in the next 50 years. Additionally, ecological risks by pesticide residues in vegetable ecosystem can be affected by various planting activities. These results will contribute to guide the rational application of pesticides and control soil environmental risks, thereby achieving the agricultural green development in the TGRA.

Aggressive angiomyxoma: The first case report in skull.

Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor primarily growing in the soft tissue of the pelvis and perineum in women of reproductive age. It is a benign tumor that still has a probability of being accompanied by localized invasion. Although negative margins of resection are difficult to achieve due to the invasive nature of the tumor and the lack of a well-defined capsule, the first line of treatment for AAM is surgery. The diagnosis of AAM is difficult to make due to a lack of specific manifestations and specific tumor markers. In this study, we reported a case of aggressive angiomyxoma in a 2-year-old girl that rarely develops in the skull with craniocerebral compression. The patient initially had a mass on her head that attracted the attention of her family, and then she began to have episodic headaches. Surgery was performed after hospitalization, and the tumor recurred 1 year after the operation, around the originally affected skull.

A Chinese Family With Cerebral Cavernous Malformation Caused by a Frameshift Mutation of the CCM1 Gene: A Case Report and Review of the Literature.

Background: Familial cerebral cavernous malformation (FCCM) is a vascular malformation disease closely linked to three identified genes: KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3. Over the past decade, a few cases of cerebral cavernous malformation (CCM) caused by different gene mutations have been reported in Chinese families. Herein, we introduce a Chinese family affected by FCCM due to a kind of KRIT1/CCM1 frameshift mutation. At the same time, a literature review was conducted to identify case reports of familial cerebral cavernous malformation. Case presentation: The proband in the family in question demonstrated a series of clinical symptoms and features, including headache and bleeding. The proband was hospitalized for headache twice and, both times was examined under suspicion of CCM and received surgical treatment. Magnetic resonance imaging results showed that the proband had multiple intracranial vascular lesions, including on the brain, brainstem, and cerebellum. Genetic test results showed that the classic KRIT1 gene in the proband had a pathogenic mutation. The family members of the proband also showed typical cerebral cavernous malformation when considering clinical manifestations, magnetic resonance imaging findings and genetic test results. Conclusions: We report a case of Chinese FCCM and its associated symptoms with CCM1-deletion mutations in China. Our findings deepen our understanding of CCM mutations and related phenotypes, the investigation results of this clinical experiment further show that the gene mutation form we reported plays an important role in human FCCM, and this trial investigation is beneficial for genetic counseling for CCM patients.

Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity.

Epilepsy, a functional disease caused by abnormal discharge of neurons, has attracted the attention of neurologists due to its complex characteristics. N6-methyladenosine (m6A) is a reversible mRNA modification that plays essential role in various biological processes. Nevertheless, no previous study has systematically evaluated the role of m6A regulators in epilepsy. Here, using gene expression screening in the Gene Expression Omnibus GSE143272, we identified seven significant m6A regulator genes in epileptic and non-epileptic patients. The random forest (RF) model was applied to the screening, and seven m6A regulators (HNRNPC, WATP, RBM15, YTHDC1, YTHDC2, CBLL1, and RBMX) were selected as the candidate genes for predicting the risk of epilepsy. A nomogram model was then established based on the seven-candidate m6A regulators. Decision curve analysis preliminarily showed that patients with epilepsy could benefit from the nomogram model. The consensus clustering method was performed to divide patients with epilepsy into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. Patients in clusterB had higher m6A scores than those in clusterA. Furthermore, the patients in each cluster had unique immune cell components and different cell death patterns. Meanwhile, based on the M6A classification, a correlation between epilepsy and glucose metabolism was laterally verified. In conclusion, the m6A regulation pattern plays a vital role in the pathogenesis of epilepsy. The research on m6A regulatory factors will play a key role in guiding the immune-related treatment, drug selection, and identification of metabolism conditions and mechanisms of epilepsy in the future.

Effect of Deep Brain Stimulation on Female Parkinsonian Patients with Lower Urinary Tract Symptoms.

PURPOSE: This study aimed to investigate the characteristics of urodynamics in female parkinsonian patients with lower urinary tract symptoms (LUTS) and evaluate the outcomes of deep brain stimulation (DBS) based on overactive bladder (OAB) scores and quality of life (QOL) scores. PATIENTS AND METHODS: Urodynamic assessment was performed in 20 female parkinsonian patients with LUTS. OAB scores and QOL scores were collected before and 6 months after DBS treatment (The target of DBS is STN). We evaluated the related factors affecting QOL score and also the changes in QOL score after DBS treatment. RESULTS: The mean age of 20 patients was 60.6±6.3 years, with 65% of patients identified with OAB in urodynamic studies. The mean OAB total score and QOL score at baseline were 7.3±3.7 and 5.0±1.1, respectively. Four items in the OAB score were found to be independent factors and they influenced the baseline QOL scores. Six months after DBS treatment, the OAB total score and the QOL score were significantly decreased (3.7±3.2 (p = 0.002) and 3.4±1.4 (p < 0.001), respectively). Improvements in OAB item 2 (nocturia) and item 3 (urgency) scores were found to be independent factors, which had an influence on the improvement in QOL scores from multivariate analysis. Improvement of OAB item 2 (nocturia) exhibited the greatest influence on improvement in the QOL score. After DBS treatment, 40% of the patients showed significant improvement in urination symptoms (≥2 points reduction in QOL score), 30% of the patients showed mild improvement (1 point reduction in QOL score), and 30% patients showed no improvement (no change in QOL score). No patients exhibited worsening urination symptoms. CONCLUSION: Most parkinsonian female patients with lower urinary tract symptoms were diagnosed with OAB. DBS treatment improved OAB symptoms. Improvement of nocturia and urgency positively impacts the QOL of female parkinsonian patients.

Pharmacokinetic difference of berberine between normal and chronic visceral hypersensitivity irritable bowel syndrome rats and its mechanism.

Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T1/2 and AUC(0-t) of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c-fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK.

Highly dispersive PdCoB catalysts for dechlorination of chlorophenols.

Highly dispersive PdCoB nano-particles were prepared by precipitation-reduction with NaBH4 at 273 K. Characterization showed that the dispersion of amorphous alloy PdCoB nano-particles increased with decrease in both Pd/Co ratio and preparation temperature. The size of PdCoB-L(273) (Pd/Co ratio of 0.0005) nano-particles prepared at 273 K was 5 nm and BET specific surface area was estimated to be 177 m(2)/g, much higher than those of bimetallic catalysts reported in literature. During the hydrodechlorination of 4-chlorophenol, PdCoB catalysts were effective within pH range from 2.5 to 11. The activity of PdCoB can be promoted by the increase in B/Co ratio on the surface. PdCoB-L(273) sample presented the highest efficiency, and the reaction constants described in different terms for 4-chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol were much higher than those obtained over PdFe in literature, probably ascribed to smaller particle sizes, less agglomerations and strong synergistic effect between Pd, Co and B species.