Exploring causal effects and potential mediating mechanisms of genetically linked environmental senses with intracerebral hemorrhage.

The occurrence mechanism of intracerebral hemorrhage remains unclear. Several recent studies have highlighted the close relationship between environmental senses and intracerebral hemorrhage, but the mechanisms of causal mediation are inconclusive. We aimed to investigate the causal relationships and potential mechanisms between environmental senses and intracerebral hemorrhage. Multiple Mendelian randomization methods were used to identify a causal relationship between environmental senses and intracerebral hemorrhage. Gut microbiota and brain imaging phenotypes were used to find possible mediators. Enrichment and molecular interaction analyses were used to identify potential mediators and molecular targets. No causal relationship between temperature and visual perception with intracerebral hemorrhage was found, whereas long-term noise was identified as a risk factor for intracerebral hemorrhage (OR 2.95, 95% CI: 1.25 to 6.93, PIVW = 0.01). The gut microbiota belonging to the class Negativicutes and the order Selenomonadales and the brain image-derived phenotypes ICA100 node 54, edge 803, edge 1149, and edge 1323 played mediating roles. "Regulation of signaling and function in synaptic organization" is the primary biological pathway of noise-induced intracerebral hemorrhage, and ARHGAP22 may be the critical gene. This study emphasized the importance of environmental noise in the prevention, disease management, and underlying biological mechanisms of intracerebral hemorrhage.

Study of prediction model for high-grade meningioma using fractal geometry combined with radiological features.

PURPOSE: To establish a prediction model combining fractal geometry and radiological features, which consider the complexity of tumour morphology advancing beyond the limitations of previous models. METHODS: A total of 227 patients at the First Affiliated Hospital of Harbin Medical University from July 2021 to November 2023 were included. Fractal geometry was calculated and the radiomics features were extracted from regions of interest (ROIs). Weighted Gene Co-Expression Network Analysis (WGCNA) was employed for preliminary screening to identify those that were significantly associated with high-grade meningioma. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression was employed for further screening the radiomics features. Area under curve (AUC) was to evaluate models' performance. RESULTS: In entire patient cohort, low-grade meningiomas had significantly lower fractal dimensions (P = 0.01), while high-grade meningiomas had higher lacunarity (P = 0.049). Fractal dimension (OR 6.8, 95% CI 1.49-36.51, P = 0.017), lacunarity (OR 3.7, 95% CI 1.36-11.75, P = 0.014), and Rscore (OR 2.8, 95% CI 1.55-5.75, P = 0.002) were independent risk factors for high-grade meningiomas. The final results demonstrated that the "fractal geometry + radiological features (semantic features + radiomics features)" model exhibited the most optimal performance in predicting high-grade meningioma, with an AUC of 0.854 in the training cohort and 0.757 in the validation cohort. CONCLUSION: Significant differences in fractal dimension and lacunarity exist between high-grade and low-grade meningiomas, which can be potential predictive factors. The developed predictive model demonstrated good performance in predicting high-grade meningiomas.

Prediction model for poor short-term prognosis in patients with chronic subdural hematoma after burr hole drainage: a retrospective cohort study.

Chronic subdural hematoma (CSDH) is a common condition in neurosurgery. With an aging population, there is increasing attention on the prognosis of patients following surgical intervention. We developed a postoperative short-term prognostic prediction model using preoperative clinical indicators, aiming to assist in perioperative medical decision-making and management. The dataset was randomly divided into training and validation cohorts. An mRS score greater than 2 one month after discharge was considered indicative of a poor prognosis. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression analysis was used for multivariate analysis to identify independent risk factors and construct a prediction nomogram for poor prognosis one month after discharge. The performance of the nomogram was assessed using the Receiver Operating Characteristic (ROC) curve and calibration curve. A Decision Curve Analysis (DCA) was also conducted to determine the net benefit threshold of the prediction model. Among the 505 participants, 18.8% (95/505) had a poor prognosis one month after discharge. The baseline characteristics did not significantly differ between the training cohort and the validation cohort. LASSO regression analysis in the training cohort reduced the predictors to four potential factors. Further multivariate logistic analyses in the training cohort identified four independent predictors: age, admission Glasgow Coma Scale (GCS) score, hemiparesis, and hemoglobin count. These predictors were incorporated into the nomogram prediction model. Internal validation using ROC analysis, calibration curves, and other methods demonstrated a strong correlation between the observed and predicted likelihood of poor prognosis one month after discharge. The visualized nomogram prediction model we developed for short-term postoperative prognosis of chronic subdural hematoma after burr hole drainage aids in predicting short-term outcomes and guiding clinical treatment decisions. Further external validation is needed in the future to confirm its effectiveness.

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

BACKGROUND: To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. METHODS: 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. RESULTS: After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). CONCLUSION: Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

A novel transformer autoencoder for multi-modal emotion recognition with incomplete data.

Multi-modal signals have become essential data for emotion recognition since they can represent emotions more comprehensively. However, in real-world environments, it is often impossible to acquire complete data on multi-modal signals, and the problem of missing modalities causes severe performance degradation in emotion recognition. Therefore, this paper represents the first attempt to use a transformer-based architecture, aiming to fill the modality-incomplete data from partially observed data for multi-modal emotion recognition (MER). Concretely, this paper proposes a novel unified model called transformer autoencoder (TAE), comprising a modality-specific hybrid transformer encoder, an inter-modality transformer encoder, and a convolutional decoder. The modality-specific hybrid transformer encoder bridges a convolutional encoder and a transformer encoder, allowing the encoder to learn local and global context information within each particular modality. The inter-modality transformer encoder builds and aligns global cross-modal correlations and models long-range contextual information with different modalities. The convolutional decoder decodes the encoding features to produce more precise recognition. Besides, a regularization term is introduced into the convolutional decoder to force the decoder to fully leverage the complete and incomplete data for emotional recognition of missing data. 96.33%, 95.64%, and 92.69% accuracies are attained on the available data of the DEAP and SEED-IV datasets, and 93.25%, 92.23%, and 81.76% accuracies are obtained on the missing data. Particularly, the model acquires a 5.61% advantage with 70% missing data, demonstrating that the model outperforms some state-of-the-art approaches in incomplete multi-modal learning.

Risk Factors for Seizures After Titanium Cranioplasty: Five-Year Experience from a Single Institution.

OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.

Human adipose-derived stem cell-loaded small intestinal submucosa as a bioactive wound dressing for the treatment of diabetic wounds in rats.

Chronic nonhealing wounds are one of the most common and serious complications of diabetes, which can lead to disability of patients. Adipose-derived stem cells (ADSCs) have emerged as a promising tool for skin wound healing, but the therapeutic potential depends considerably on the cell delivery system. Small intestinal submucosa (SIS) is an extracellular matrix-based membranous scaffold with outstanding repair potential for skin wounds. In this study, we first fabricated a bioactive wound dressing, termed the SIS+ADSCs composite, by using human ADSCs as the seed cell and porcine SIS as the cell delivery vehicle. Then, we systematically investigated, for the first time, the healing potential of this wound dressing in a rat model of type 2 diabetes. In vitro studies revealed that SIS provided a favorable microenvironment for ADSCs and significantly promoted the expression of growth factors critical for chronic wound healing. After implantation in the full-thickness skin wounds of diabetic rats, the SIS+ADSCs composite showed a higher wound healing rate and wound healing quality than those in the PBS, ADSCs, and SIS groups. Along with the ability to modulate the polarization of macrophages in vivo, the SIS+ADSCs composite was potent at promoting wound angiogenesis, reepithelialization, and skin appendage regeneration. Taken together, these results indicate that the SIS+ADSCs composite has good therapeutic potential and high translational value for diabetic wound treatment.

Cloning, sequence analysis and expression of bacterial lipase-coding DNA fragments from environment in Escherichia coli.

Thirteen pairs of primers were designed, synthesized and used to clone the whole coding sequences or mature peptide-coding sequences of lipases. Bacteria producing extracellular lipases were enriched for the extraction of total DNAs. Eight fragments with 500-1,200 bp in length were obtained by using touchdown PCR and sequenced. Five of them were found to be lipase-coding DNAs. One fragment called BL9 that was 95.9% similar to a coding sequence of putative lipase. This lipase contained a Gly-His-Ser-Met-Gly motif which is matched to the consensus Gly-X-Ser-X-Gly conserved among lipolytic enzymes. The BL9 DNA fragment was inserted into the expression vector pET32a(+) of Escherichia coli. A functional product was yielded in the supernatant and produced a hydrolyzed zone on the tributyrin agar.

Cloning, sequence, and function analyses of giant panda (Ailuropoda melanoleuca) CD9 gene.

CD9 is a member of the tetraspanin family proteins and has recently been shown to be essential for sperm-oocyte fusion in mice. The giant panda (Ailuropoda melanoleuca) CD9 (gpCD9) cDNA was amplified for the first time by RT-PCR from ovary total RNA and cloned, sequenced and analyzed. The result revealed that the open reading frame (ORF) of gpCD9 was 681 bp, which has the same length as that of mouse. Sequence analysis and structure prediction displayed that the amino acid sequence of gpCD9 is over 80% identity to those of mammals with the conserved structures, including the four transmembrane domains (TM) and certain characteristic residues. The results of sperm-egg fusion experiments demonstrated that giant panda CD9 large extracellular loop (LEL) significantly inhibited (P < 0.05) the mouse gamete fusion when the recombinant protein was added. However, when three amino acid residues TVT (173-175) of the gpCD9 were mutated to AAA, the large extracellular loop (LELM) of mutated protein was rarely inhibiting the gamete fusion of mice. Our results may be useful in improving an insight into understanding the potential mechanism of gamete fusion and genetic characteristics of giant panda.

Mesenchymal Stem Cells in Combination with Hyaluronic Acid for Articular Cartilage Defects.

Mesenchymal stem cells (MSCs) and hyaluronic acid (HA) have been found in previous studies to have great potential for medical use. This study aimed to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) combined with HA on articular cartilage repair in canines. Twenty-four healthy canines (48 knee-joints), male or female with weight ranging from 5 to 6 kg, were operated on to induce cartilage defect model and divided into 3 groups randomly which received different treatments: BMSCs plus HA (BMSCs-HA), HA alone, and saline. Twenty-eight weeks after treatment, all canines were sacrificed and analyzed by gross appearance, magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining, Masson staining, toluidine blue staining, type II collagen immunohistochemistry, gross grading scale and histological scores. MSCs plus HA regenerated more cartilage-like tissue than did HA alone or saline. According to the macroscopic evaluation and histological assessment score, treatment with MSCs plus HA also lead to significant improvement in cartilage defects compared to those in the other 2 treatment groups (P < 0.05). These findings suggested that allogeneic BMSCs plus HA rather than HA alone was effective in promoting the formation of cartilage-like tissue for repairing cartilage defect in canines.

Development of a Xeno-Free Feeder-Layer System from Human Umbilical Cord Mesenchymal Stem Cells for Prolonged Expansion of Human Induced Pluripotent Stem Cells in Culture.

Various feeder layers have been extensively applied to support the prolonged growth of human pluripotent stem cells (hPSCs) for in vitro cultures. Among them, mouse embryonic fibroblast (MEF) and mouse fibroblast cell line (SNL) are most commonly used feeder cells for hPSCs culture. However, these feeder layers from animal usually cause immunogenic contaminations, which compromises the potential of hPSCs in clinical applications. In the present study, we tested human umbilical cord mesenchymal stem cells (hUC-MSCs) as a potent xeno-free feeder system for maintaining human induced pluripotent stem cells (hiPSCs). The hUC-MSCs showed characteristics of MSCs in xeno-free culture condition. On the mitomycin-treated hUC-MSCs feeder, hiPSCs maintained the features of undifferentiated human embryonic stem cells (hESCs), such as low efficiency of spontaneous differentiation, stable expression of stemness markers, maintenance of normal karyotypes, in vitro pluripotency and in vivo ability to form teratomas, even after a prolonged culture of more than 30 passages. Our study indicates that the xeno-free culture system may be a good candidate for growth and expansion of hiPSCs as the stepping stone for stem cell research to further develop better and safer stem cells.

[COMPARISON OF TWO ANIMAL MODELS WITH CARTILAGE DEFECT].

OBJECTIVE: To compare difference in the establishment of animal model of cartilage defect by resection of medial collateral ligament and meniscus and by cartilage excavation so as to provide a proper way for the choose of animal model preparation of catilage defect. METHODS: Ten healthy beagles, male or female, weighing 5.0-10.0 kg, were randomly divided into 3 groups. Resection of knee collateral ligament and meniscus was performed on 4 beagles of group A, cartilage excavation of knee-joints in 4 beagles of group B, and no treatment on 2 beagles of group C as controls. At 16 weeks after modeling, MRI, gross observation, HE staining, Safranin O staining, and toluidine blue staining were performed, and Osteoarthritis Research Society International (OARSI) score was recorded. RESULTS: MRI and histology observation showed no obvious cartilage defect in group A; obvious cartilage defects were observed in group B and gross observation showed dramatic dark red cartilage defects. OARSI score was significantly lower in group A (0.940±0.574) than group B (4.500±0.516) (t=18.461, P=0.000). CONCLUSIONS: The cartilage excavation is better than resection of both meniscus and medial collateral ligament, which provides a good method of establishing an animal model of cartilage defect at 16 weeks after operation.

Placenta- versus bone-marrow-derived mesenchymal cells for the repair of segmental bone defects in a rabbit model.

Tissue-engineered bones (TEBs) constructed with bone-marrow-derived mesenchymal stem cells (BMSCs) seeded on biomaterial scaffolds have achieved good results for bone defect repair in both animal experiments and clinical trials. This has been limited, however, by the source and quantity of BMSCs. We here explored TEBs constructed by placenta-derived mesenchymal stem cells (PMSCs) and compared their effect for the repair of critical-sized segmental osteoperiosteal defects with TEBs constructed with BMSCs. PMSCs were isolated from rabbit placenta by gradient centrifugation and in vitro monolayer culturing, and BMSCs were isolated from the hindlimb bone marrow of newborn rabbit. Primary cultured PMSCs and BMSCs were uniformly in a spindle shape. Immunocytochemistry indicated that both types of cells are positive for CD44 and CD105, and negative for CD34 and CD40L, confirming that they are mesenchymal stem cells. BrdU-labeled PMSCs and BMSCs were respectively co-cultured with bio-derived bone materials to construct TEBs in vitro. Critical-sized segmental osteoperiosteal defects of radii were created in 24 rabbits by surgery. The defects were repaired with TEBs constructed with PMSCs and BMSCs. The results showed that TEBs constructed by both PMSCs and BMSCs could repair the osteoperiosteal defects in a 'multipoint' manner. Measurement of radiography, histology, immunohistochemistry, alkaline phosphatase activity, osteocalcin assaying and biomechanical properties have found no significant difference between the two groups at 2, 4, 8 and 12 weeks after the transplantation (P > 0.05). Taken together, our results indicate that PMSCs have similar biological characteristics and osteogenic capacity to BMSCs and can be used as a new source of seeding cells for TEBs.

[Effect of copper-ion on proliferation and differentiation of vascular endothelial cells].

OBJECTIVE: To evaluate the effect of copper-ion on the proliferation and differentiation of human umbilical vein endothelial cell (HUVEC). METHODS: HUVEC were cultured and passaged in vitro. HUVEC were inoculated into 96-well plate with density of 5 x 10(3)/well. All the cells were divided into 3 groups randomly according to different culture mediums: group A (5 micromol/L CuSO4), group B (25 micromol/L CuSO4), group C (control group). Every group had 4 wells, and the basic culture medium was MCDB131. The cell growth curves of 3 groups were drawn by using MTT. HUVEC were inoculated into 6-well plate with density of 2 x 10(5)/well. Grouping of the cells was the same as the above. The gene expressions of endothelial nitric oxide synthase (eNOS) and tyrosine kinase with immunoglobulin-like and EGF-like domain 1 (Tie-1) were detected by real-time RT-PCR. RESULTS: The growth curves revealed that the exponential growth time was the first 3 days, plateau growth time begun on the 4th day. The proliferation of group A was stronger than that of groups B and C from the 3rd day, within 2 days, the proliferation of group B was stronger than that of group C; however, it decreased and was weaker than group C from the 4th day, all showing statistically significant difference (P < 0.05). The results of real-time RT-PCR revealed that the expressions of eNOS in groups A, B and C were 7.294 +/- 1.488, 0.149 +/- 0.044 and 1.000 +/- 0.253; and the expressions of Tie-1 in groups A, B and C were 1.481 +/- 0.137, 1.131 +/- 0.191 and 1.000 +/- 0.177. Group A compared with groups B and C, both of 2 genes were up-regulated (P < 0.05). Group B compared with group C, eNOS was down-regulated (P < 0.05) and the difference of Tie-1 expression was not statistically significant (P > 0.05). CONCLUSION: 5 micromol/L copper-ion can promote the proliferation and differentiation of HUVEC effectively.