The use of human-derived feeder layers for the cultivation of transplantable human epidermal cell sheet to repair second degree burn wounds.

BACKGROUND AND OBJECTIVES: Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human. MATERIALS AND METHODS: Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6). RESULTS: Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group. CONCLUSIONS: Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process.

Wnt4-modified NSC transplantation promotes functional recovery after spinal cord injury.

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, yet there are no effective therapies currently due to the failure of reconstructing the interruption of the neuroanatomical circuit. While neural stem cell (NSC) transplantation has been considered a potential strategy to repair the neural circuit after SCI, the efficacy of this strategy remains unproven. The main reason is that most of the transplanted NSC differentiates into astrocyte rather than neuron in the microenvironment of SCI. Our results demonstrated that Wnt4 significantly promotes the differentiation of NSC into neuron by activating both ß-catenin and MAPK/JNK pathways and suppressing the activation of Notch signaling, which is acknowledged as prevention of NSC differentiation into neuron, through downregulating NICD expression, translocating and preventing the combination of NICD and RbpJ in nucleus. In addition, Wnt4 rescues the negative effect of Jagged, the ligand of Notch signaling, to promote neuronal differentiation. Moreover, in vivo study, transplantation of Wnt4-modified NSC efficaciously repairs the injured spinal cord and recovers the motor function of hind limbs after SCI. This study sheds new light into mechanisms that Wnt4-modified NSC transplantation is sufficient to repair the injured spinal cord and recover the motor dysfunction after SCI.

Epidemiological characteristics and risk factors of syphilis among blood donors in Huzhou.

OBJECTIVE: To investigate the epidemiological characteristics and risk factors for syphilis in Huzhou City, and to provide data to support the design of more effective health counselling and screening measures for blood donors. METHODS: A retrospective study was conducted to analyse the demographic characteristics and seropositivity of syphilis among blood donors from 2019 to 2021. The differences in the serological status of syphilis among different populations under different demographic factors were compared, and conditional logistic regression analysis was used to identify the risk factors for syphilis. RESULTS: The seropositivity rate of syphilis among blood donors in Huzhou City was 133/100,000, which decreased year by year. There were significant differences in the syphilis seropositivity rate among different groups in terms of age, education level, occupation, household registration, marital status and blood donation history (P < 0.05). The multivariate logistic regression model showed that all six factors, including age, education level, occupation, household registration, marital status and blood donation history, had significant effects on syphilis infection (P < 0.01), with OR values and 95% CIs of 2. 387 (1.381-4.127), 3.607 (1.609-8.086), 2.784 (1.657-4.679), 5.074 (1.865-13.804), 11.177 (3.481-35.888), and 11.244 (3.940-32.091), respectively. CONCLUSION: There is room for improvement in pre-donation health counselling and screening of high-risk populations. Timely monitoring and updating of demographic data for specific high-risk populations is essential.

The influence of demographic and lifestyle factors on blood donation delay among student population: a retrospective study.

Objective: This study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate. Methods: Data on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed. Results: The deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% (p = 0.000, 95%CI: 12.14-13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92-5.53%), BP 3.30% (3.06-3.55%), and Hb 2.92% (2.68-3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate (p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals (p < 0.05). Logistic regression showed that sex, blood donation history, sleep quality, diet and mental status were independent risk factors for ALT deferral (p < 0.05), with odds ratios (ORs) of 5.057, 2.735, 1.594, 3.679, and 1.957, respectively. Age, blood donation history, sleep quality and mental state were independent risk factors for BP deferral (p < 0.05), with ORs of 0.256, 3.658, 6.042, and 1.812, respectively. Gender, blood donation history and diet were independent risk factors for Hb deferral (p < 0.05), with ORs of 0.244, 0.542, and 3.103, respectively. Conclusion: Students' health problems require attention. Effective health education should improve self-health management and pre-donation health behaviour to encourage regular blood donation.

Effect of different cooking water on flavor characteristics of mutton soup.

The mutton flavor is affected by cooking water significantly, and the flavor of mutton is delicious and widely loved by consumers through an extremely simple processing in northwest China, such as Inner Mongolia, Ningxia, and Xinjiang. The flavor shows obvious changes if get out of these areas even use the same raw meat, which may be caused by different cooking water. To determine whether and how the cooking water affect the mutton soup flavor, the elements in water, the flavor was studied by inductively coupled plasma mass spectrometry (ICP-MS), amino acid analyzer, and thermal desorption (TDS)-gas chromatography-mass spectrometry (GC-MS). Specifically, three water samples from different sources, Ningxia (NXW), Beijing (BJW), and ultrapure water from the laboratory (PUW), were used for cooking with Tan sheep's ribs to get different mutton soups. The inductively coupled plasma mass spectrometry (ICP-MS) results showed that the elements and the concentration of solutes in different water sources were significantly different. The NXW batch had the highest Na, Mg, K, and Sr concentrations, and Na in NXW water reached to 50.60 mg/L, which existed as Na+, significantly (p < .05) higher than BJW (8.63 mg/L) and PUW, which were important to the flavor of mutton soup. The PUW batch had the highest content of free amino acids, and the content of glutamic acid (Glu) reached to 17.89 µg/mL. The NXW batch had the highest content of taste nucleotides, and the content of 5´-IMP reached to 68.68 µg/ml. The volatiles of the three batches had significant differences, and only 40 volatiles were detected in all batches. Further flavor studies using electronic nose and electronic tongue showed significant differences in overall aroma and overall taste, especially bitterness, saltiness, and astringency. The results could provide a basis for improving the flavor quality for the mutton soup.

Pretreatment of Sulfonylureas Reducing Perihematomal Edema in Diabetic Patients With Basal Ganglia Hemorrhage: A Retrospective Case-Control Study.

Background: The sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel is a target key mediator of brain edema. Sulfonylureas (SFUs) are blockers of the SUR1-TRPM4 channel. We made two assessments for the pretreatment of SFUs: (1) whether it associates with lower perihematomal edema (PHE) and (2) whether it associates with improved clinical outcomes in diabetic patients who have acute basal ganglia hemorrhage. Methods: This retrospective case-control study was conducted in diabetic adults receiving regular SFUs before the onset of intracerebral hemorrhage (ICH). All of the patients received the clinical diagnosis of spontaneous basal ganglia hemorrhage. The diagnosis was confirmed by a CT scan within 7 days after hemorrhage. For each case, we selected two matched controls with basal ganglia hemorrhage based on admission time (≤5 years) and age differences (≤5 years), with the same gender and similar hematoma volume. The primary outcome was PHE volume, and the secondary outcomes were relative PHE (rPHE), functional independence according to modified Rankin Scale score and Barthel Index at discharge, and death rate in the hospital. Results: A total of 27 patients (nine cases and 18 matched controls), admitted between January 1, 2009 and October 31, 2018, were included in our study. There was no significant association between SFU patients and non-SFU patients on PHE volumes [15.4 (7.4-50.2 ml) vs. 8.0 (3.1-22.1) ml, p = 0.100]. Compared to non-SFU patients, the SFU patients had significantly lower rPHE [0.8 (0.7-1.3) vs. 1.5 (1.2-1.9), p = 0.006]. After we adjusted the confounding factors, we found that sulfonylureas can significantly reduce both PHE volume (regression coefficient: -13.607, 95% CI: -26.185 to -1.029, p = 0.035) and rPHE (regression coefficient: -0.566, 95% CI: -0.971 to -0.161, p = 0.009). However, we found no significant improvement in clinical outcomes at discharge, in the event of pretreatment of SFUs before the onset of ICH, even after we adjusted the confounding factors. Conclusion: For diabetic patients with acute basal ganglia hemorrhage, pretreatment of sulfonylureas may associate with lower PHE and relative PHE on admission. No significant effect was found on the clinical outcomes when the patients were discharged. Future studies are needed to assess the potential clinical benefits using sulfonylureas for ICH patients.

Identification of a new function of metallothionein-like gene OsMT1e for cadmium detoxification and potential phytoremediation.

Cadmium (Cd) is a biologically non-essential and toxic heavy metal leaking to the environment via natural emission or anthropogenic activities, thereby contaminating crops and threatening human health. Metallothioneins (MTs) are a group of metal-binding proteins playing critical roles in metal allocation and homeostasis. In this study, we identified a novel function of OsMT1e from rice plants. OsMT1e was dominantly expressed in roots at all developmental stages and, to less extent, expressed in leaves at vegetative and seed filling stages. OsMT1e was mainly targeted to the nucleus and substantially induced by Cd exposure. Expression of OsMT1e in a yeast Cd-sensitive strain ycf1 conferred cellular tolerance to Cd, even though the ycf1 + OsMT1e cells accumulated more Cd than the control cells (ycf1 + pYES2). Both transgenic rice overexpressing (OX) and repressing OsMT1e by RNA interference (RNAi) were developed. Phenotypic analysis revealed that OsMT1e overexpression enhanced the rice growth concerning the increased shoot or root elongation, dry weight and chlorophyll contents, whereas the RNAi lines displayed a sensitive growth phenotype compared to wild-type. Assessment with 0.5, 2 and 10 µM Cd for two weeks revealed that the RNAi lines accumulated less Cd, while the OX lines had an increased Cd accumulation in root and shoot tissues. The contrasting Cd accumulation phenotypes between the OX and RNAi lines were further confirmed by a long-term study with 0.5 µM Cd for one month. Overall, the study unveiled a new function of OsMT1e in rice, which can be potentially used for engineering genotypes for phytoremediation or minimizing Cd in rice crops.

High mobility group box 1 antibody represses autophagy and alleviates hippocampus damage in pilocarpine-induced mouse epilepsy model.

As a neurological disorder, epilepsy has affected over 65 million people all over the world because of the unforeseeable seizures it might cause. However, in-depth understandings of the pathogenesis of epilepsy and effective treatments for the disease are still lacked. Recent discoveries suggest that autophagy, as an endogenous self-cleansing pathway in mammals, might be involved in the onset of epilepsy. Our study assumes that a non-histone DNA binding protein, high mobility group box-1 (HMGB1), formerly considered as a crucial inflammatory factor, may mediate the autophagy of neurons in epileptic mouse brain. To verify this hypothesis, pilocarpine induced epilepsy mouse model was constructed. The mice were treated with HMGB1 antibody for 4 weeks after the initial epileptic seizure. Behavioral test results suggested a recovery of learning ability and memory in epileptic mice when treated with HMGB1 antibody. Pathological changes in hippocampus were inspected under microscopes and hippocampus damages caused by seizures in mouse with epilepsy such as increased intracellular space were alleviated by HMGB1 antibody treatment. Moreover, the expressions of the proteins involved in autophagy pathways were detected by immunofluorescence staining and western blot. microtubule-associated protein 1A/1B-light chain 3 (LC3), Beclin 1, autophagy protein-5 (ATG5), and ATG7 levels were significantly decreased by HMGB1 antibody while the level of p62 was increased. TdT-mediated dUTP Nick-End Labeling (TUNEL) illustrated that cell apoptosis induced by seizures in hippocampus was mitigated by HMGB1 antibody. In conclusion, we propose that HMGB1 may induce increased autophagy in epilepsy mouse model.

Liraglutide attenuates the depressive- and anxiety-like behaviour in the corticosterone induced depression model via improving hippocampal neural plasticity.

Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing. However, whether liraglutide is an effective antidepressant remains unknown. Therefore, we tested this hypothesis in the depression model of chronic administration of corticosterone (CORT) in mice and treated the animals daily with liraglutide (5 or 20 nmol/kg ip.) to assess its therapeutic potential as an antidepressant. Behavioral studies showed that liraglutide administration attenuated depressive- and anxiety- like behaviors in this depression mouse model, and attenuated the hyperactivity induced by the stress hormone. Additionally, liraglutide treatment protected synaptic plasticity and reversed the suppression of hippocampal long-term potentiation induced by CORT administration, demonstrating synaptic protective effects of liraglutide. We also found that liraglutide treatment increased the cell density of immature neurons in the subgranular dentate gyrus region of the hippocampus. In addition, liraglutide prevented the CORT induced impairments and simultaneously increased the level of phosphorylated GSK3ß in the hippocampus, which may be instrumental in the anti-depressant activity of liraglutide treatment. Taken together, liraglutide has the potential to act as a therapeutic treatment of depression.

Monitoring and detection of leprosy patients in Southwest China: A retrospective study, 2010-2014.

More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Correlation analysis of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in refractory chronic rhinosinusitis: A retrospective study

Objective: To investigate the potential correlation of transforming growth factor-β (TGF-β), matrix metalloprotein 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), Interleukin 1 (IL-1), IL-4, IL-6, IL-17, and tumor necrosis factor alpha (TNF-α) in refractory chronic rhinosinusitis.Methods: A total of 150 participants were retrospectively included in this study from August 2018 to February 2020. The people enrolled were equally allocated into refractory group (patients with refractory chronic rhinosinusitis), chronic group (patients with chronic rhinosi-nusitis), and control group (normal people). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α were recorded. The unconditional multivariate binary logistic regression was used to analyze the factors affecting refractory chronic rhinosinusitis.Results: The Davos score, T&T olfactometer threshold test, and Lund-Mackay CT scores in refractory group were significantly higher than the chronic group (P<0.05). The level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α in the refractory group were significantly higher than the chronic group and the control group (all P<0.05). Similarly, the level of the above mentioned indexes in the chronic group were significantly higher than the control group (P<0.05). The Davos score, T&T olfactometer threshold test score, Lund-Mackay CT score, and the level of TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α positively correlated with refractory chronic rhinosinusitis. Moreover, the unconditional multivariate binary logistic regression showed that the influencing factors of refractory chronic rhinosinusitis included TGF-β1, MMP-9, TIMP-1, IL-1, IL-4, IL-6, IL-17, and TNF-α.Conclusion: The findings of the present study provide evidence for TGF-β1, MMP-9, TIMP-1, IL-4, IL-6, IL-17, and TNF-α as the influencing factors of refractory chronic rhinosinusitis (AU)

[Building a SAN and NAS integrated storage system in hospitals].

We have recentely built a cluster and backup system based on a SAN + NAS integrated storage system at a low price. The integration of SAN + NAS provides a storage system of fine quality, high reliability and high stability for hospitals. The article mainly introduces the choice of the project, the design of SAN + NAS integration and its implementation.

Readmission rate after coronary artery bypass grafting versus percutaneous coronary intervention for unprotected left main coronary artery narrowing.

Many studies have reported comparable risk of hard end points between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) stenosis. However, there are limited data regarding the morbidity associated with ULMCA revascularization. This study sought to compare the cause and risk of readmissions after PCI and CABG for ULMCA stenosis. We evaluated the unadjusted and adjusted risk of readmissions in 1,352 patients (783 PCI treated and 569 CABG treated) who were consecutively enrolled in a multicenter registry of patients with ULMCA stenosis, named the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease trial. Overall, 206 PCI-treated patients (26.3%) experienced at least 1 readmission after the index procedure during 48.7 ± 16.0 months of follow-up compared with 84 CABG-treated patients (14.8%, p <0.001). The most frequent causes of readmission were repeat revascularization after PCI (41%) and noncardiac readmissions after CABG (48%). Through repeated events analysis, PCI was associated with more frequent readmissions than CABG (hazard ratio 2.037, 95% confidence interval 1.542 to 2.692, p <0.001), being an independent predictor of readmission (hazard ratio 1.820, 95% confidence interval 1.420 to 2.331, p <0.001). Except for the acute period, defined as the first 3 months, when there was no significant difference in readmission rate, a higher readmission rate after PCI was consistently observed over the remainder of the follow-up period. In conclusion, PCI was shown to be associated with a higher risk of readmission than CABG in treating ULMCA disease. This higher risk was attributable to more frequent revascularization in the PCI group.