Increased Accumulation of α-Synuclein in Inflamed Appendices of Parkinson's Disease Patients.

BACKGROUND: The accumulation of α-synuclein (α-Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α-Syn, and appendectomy has been reported to affect the incidence of PD. OBJECTIVE: This study investigated appendix abnormality in patients with PD. METHODS: We assessed appendix morphology in 100 patients with PD and 50 control subjects by multislice spiral computed tomography. We analyzed the clinical characteristics of patients with PD with diseased appendices, which was confirmed in seven patients by histopathological analysis. RESULTS: Chronic appendicitis-like lesions were detected in 53% of patients with PD, but these were not associated with the duration of motor symptoms. Appendicitis-like lesions, impaired olfaction, and rapid eye movement sleep behavior disorder were risk factors for PD. The following clinical symptoms could be used to identify patients with PD with appendicitis-like lesions: first motor symptoms were bradykinesia/rigidity, onset of motor symptoms in the central axis or left limb, prodromal constipation, high ratio of Unified Parkinson's Disease Rating Scale Part III score to symptom duration, low Montreal Cognitive Assessment score, and high Epworth Sleepiness Scale score. The seven patients with PD who were diagnosed with chronic appendicitis underwent appendectomy, and histopathological analysis revealed structural changes associated with chronic appendicitis and α-Syn aggregation. CONCLUSIONS: These results indicate an association between chronic appendicitis-like lesions and PD, and suggest that α-Syn accumulation in the diseased appendix occurs in PD. © 2021 International Parkinson and Movement Disorder Society.

A Survey of Aesthetic Standards of the Ear.

BACKGROUND: The aesthetic standards of the ear are very important for evaluation of auricular surgery. Few studies have previously assessed ear aesthetics, especially in China. This study aimed to investigate aesthetic standards of the ear in a Chinese population. MATERIALS AND METHODS: A questionnaire was administered to Chinese individuals, which included assessment of the general impressions of the ear and other facial aesthetic units, the individual aesthetic subunits of the ear, the effects of different ear subunits on ear symmetry and the degree of the subunits to which the participants wanted to change. Answers were recorded on a five-point Likert-style scale. Statistical analysis was performed using SPSS ver. 17.0. RESULTS: A total of 319 responses were received, 50.3% women and 49.7% men. The external ear received the lowest degree of attention either on the front or on the lateral view of the face in both genders. Among the individual aesthetic units, the earlobe received the most attention and the fine structures the lowest. The helix had the greatest effect on the ear symmetry. The structure that participants most wanted to change was the earlobe in males and the helix in females. There were significant differences on the evaluation of the helix and crus of helix among the groups divided according to educational background (P < 0.001). CONCLUSION: The results showed that the structures that people were most concerned about were the helix and earlobe. There were gender differences in the results which were also influenced by education background.

Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors.

BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPi), coupled to a DNA damaging agent is a promising approach to treating triple negative breast cancer (TNBC). However, not all patients respond; we hypothesize that non-response in some patients may be due to insufficient drug penetration. As a first step to testing this hypothesis, we quantified and visualized veliparib and carboplatin penetration in mouse xenograft TNBCs and patient blood samples. METHODS: MDA-MB-231, HCC70 or MDA-MB-436 human TNBC cells were implanted in 41 beige SCID mice. Low dose (20 mg/kg) or high dose (60 mg/kg) veliparib was given three times daily for three days, with carboplatin (60 mg/kg) administered twice. In addition, blood samples were analyzed from 19 patients from a phase 1 study of carboplatin + PARPi talazoparib. Veliparib and carboplatin was quantified using liquid chromatography-mass spectrometry (LC-MS). Veliparib tissue penetration was visualized using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) and platinum adducts (covalent nuclear DNA-binding) were quantified using inductively coupled plasma-mass spectrometry (ICP-MS). Pharmacokinetic modeling and Pearson's correlation were used to explore associations between concentrations in plasma, tumor cells and peripheral blood mononuclear cells (PBMCs). RESULTS: Veliparib penetration in xenograft tumors was highly heterogeneous between and within tumors. Only 35% (CI 95% 26-44%), 74% (40-97%) and 46% (9-37%) of veliparib observed in plasma penetrated into MDA-MB-231, HCC70 and MDA-MB-436 cell-based xenografts, respectively. Within tumors, penetration heterogeneity was larger with the 60 mg/kg compared to the 20 mg/kg dose (RSD 155% versus 255%, P = 0.001). These tumor concentrations were predicted similar to clinical dosing levels, but predicted tumor concentrations were below half maximal concentration values as threshold of response. Xenograft veliparib concentrations correlated positively with platinum adduct formation (R 2 = 0.657), but no PARPi-platinum interaction was observed in patients' PBMCs. Platinum adduct formation was significantly higher in five gBRCA carriers (ratio of platinum in DNA in PBMCs/plasma 0.64% (IQR 0.60-1.16%) compared to nine non-carriers (ratio 0.29% (IQR 0.21-0.66%, P < 0.0001). CONCLUSIONS: PARPi/platinum tumor penetration can be measured by MALDI-MSI and ICP-MS in PBMCs and fresh frozen, OCT embedded core needle biopsies. Large variability in platinum adduct formation and spatial heterogeneity in veliparib distribution may lead to insufficient drug exposure in select cell populations.

Effect of chemical aging on phosphate adsorption and ecotoxicological properties of magnesium-modified biochar.

Using magnesium-biochar composites (Mg-BC) in adsorption allows for the efficient and economically relevant removal of phosphate (PO43-) from water and wastewater. Applying Mg-BC for pollutant removal requires evaluating the adsorption capacity of composites and their ecotoxicological properties. Investigating the composite aging during the application of these composites into the soil is also essential. In the present study, nonaged and aged (at 60 or 90 °C) Mg-BC composites were investigated in the context of pyrolysis temperature (500 or 700 °C). All analyzed biochars were examined by Fourier transform infrared spectroscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and surface area. The content of polycyclic aromatic hydrocarbons (PAHs) (bioavailable Cfree and organic solvent-extractable Ctot), heavy metals (HMs), and environmentally persistent free radicals (EPFRs) were determined. Ecotoxicity was evaluated using tests with Folsomia candida and Allivibrio fischeri. The dependence of adsorption on pyrolysis temperature and composite aging time was observed. Changes in physicochemical properties occurring as a result of aging reduced the adsorption of PO43- on Mg-BC composites. It was found that nonaged Mg-BC700 was more effective (9.55 mg g -1) in the adsorption of PO43- than Mg-BC500 (5.75 mg g-1). The adsorption capacities of aged composites were from 21 to 61% lower than those of the nonaged composites. Due to aging, the content of Cfree PAHs increased by 3-5 times depending on the pyrolysis temperature. However, aging reduced the Ctot PAHs in all composites from 24 to 35% depending on the pyrolysis temperature. Ecotoxicological evaluation of Mg-BC composites showed increased toxicity after aging to both organisms. The use of aged BC potentially increases the contaminant content and toxicity of Mg-BC composites.

Effects of whole nutritional formula foods on nutritional improvement and intestinal flora in malnourished rats.

Food for special medical purposes (FSMP) has received increasing attention as an enteral nutritional supplement. To investigate the effects of whole nutritional formula (WNF) containing dietary fiber and regular formula on nutritional supplementation and improvement of intestinal microecology, a rat malnutrition model was established with the formulations of WNF, FOS, and SDF (10, 20 g/kg bw) administered by gavage for 30 days. The results showed that the three formulations effectively improved the nutritional status of the malnourished rats, significantly increasing the level of IgG, increasing the abundance of Bacteroidetes, and affecting the content of propionic acid (PRO). The nutritional status of rats is closely related to growth performance, nutritional indexes, and immunoglobulin index, which cause changes in the composition of the intestinal flora. The above results showed that WNF positively affected the nutritional improvement, immune level, and intestinal health of rats. The comprehensive evaluation also suggested that the formulation containing ginseng water-soluble dietary fiber (ginseng-SDF) had the most significant effect.

A biocompatible double-crosslinked gelatin/ sodium alginate/dopamine/quaterniazed chitosan hydrogel for wound dressings based on 3D bioprinting technology.

438Severe skin injuries can cause serious problems, which could affect the patient's normal life, if not dealt properly in a timely and effective manner. It is an urgent requirement to develop personalized wound dressings with excellent antibacterial activity and biocompatibility to match the shape of the wound to facilitate clinical application. In this study, a bioink (GAQ) based on gelatin (Gel)/sodium alginate (SA)/ quaternized chitosan (QCS) was prepared, and GAQ hydrogel dressing grafting with dopamine (GADQ) was fabricated by an extrusion three-dimensional (3D) printing technology. QCS was synthesized by modifying quaternary ammonium group on chitosan, and its structure was successfully characterized by nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Our results showed that the GADQ hydrogel dressing that was double-crosslinked by EDC/ NHS and Ca2+ had good tensile strength, considerable swelling ratio, and effective antioxidation properties. It also showed that GADQ1.5% had 93.17% and 91.06% antibacterial activity against Staphylococcus aureus and Escherichia coli, respectively. Furthermore, the relative survival ratios of fibroblast cells seeded on these hydrogels exceeded 350% after cultured for 7 days, which proved the biocompatibility of these hydrogels. Overall, this advanced 3D-printed GADQ1.5% hydrogels with effective antioxidation, excellent antibacterial activity and good biocompatibility had a considerable application potential for wound healing.

An improved surgical instrument without coupled motions that can be used in robotic-assisted minimally invasive surgery.

In order to enhance the dexterity of surgical instruments in robotic-assisted minimally invasive surgery, the robot is generally configured so as to have a wrist. However, this configuration has a problem in that there is a coupling of the motions of the wrist and the end-effector. In this paper an improved surgical instrument is proposed that eliminates the coupled motion using a compensation mechanism. The design concept behind the compensation mechanism can be applied to other types of surgical instruments. The performance of the proposed surgical instrument is validated by mechanical performance testing and animal experiments, which indicate that the problem of the coupled motion is successfully solved and the instrument is able to perform surgical tasks.

Preparation of deer oil powder and its effect on acute gastric mucosal injury in rats.

In this paper, deer oil was used as a raw material to prepare deer oil powder by microencapsulation technology to study the potential protective activity of deer oil powder on ethanol-induced acute gastric mucosal injury in rats. The results show that the best process for preparing deer oil powder is: the solids account for 25% of the system content, the wall material Whey Milk Protein Isolate-Maltodextrin ratio is 1:5, the Sodium Stearyl Lactate-Glycerides of Monostearate and Distearate compound emulsifier content is 0.8%, the ratio is 1:1, and the deer oil accounts for 30% of the solid content, and the spray drying inlet temperature is 180°C. Deer oil powder can reduce total stomach injury, gastric mucosal congestion area, and injury score index. Without affecting the blood lipid level, it can reduce the content of Myeloperoxidase, enhance the activity of Superoxide Dismutase and Glutathione Peroxidase, and has good antioxidant activity. Enhance the expression of defense factors Estradiol, Epidermal Growth Factor, and Somatostatin. At the same time, it reduces the levels of Interleukin-1ß and Interleukin-6 pro-inflammatory cytokines in gastric tissue and enhances the expression of anti-inflammatory factors Interleukin-4 and Interleukin-10. These results indicate that the gastric protection mechanism of deer oil powder may be related to the enhancement of mucosal defense factors, inhibition of inflammation, and oxidative stress. PRACTICAL APPLICATIONS: This study screened the optimal formula for preparing microencapsulated deer oil powder and proved for the first time that deer oil powder has a strong gastroprotective effect on ethanol-induced acute gastric injury in rats. The gastric protective mechanism of deer oil powder is mainly to reduce oxidative stress, inflammatory cytokine accumulation and to increase the content of defense factors. Therefore, deer oil powder can be used as a new source of gastric treatment drugs.

Panax quinquefolius Polysaccharides Ameliorate Antibiotic-Associated Diarrhoea Induced by Lincomycin Hydrochloride in Rats via the MAPK Signaling Pathways.

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.

The characterization, cytotoxicity, macrophage response and tissue regeneration of decellularized cartilage in costal cartilage defects.

After harvesting multiple costal cartilages, the local defect disrupts the integrity of the chest wall and may lead to obvious thoracic complications, such as local depression and asymmetry of the bilateral thoracic height. Decellularized materials have been used for tissue reconstruction in clinical surgeries. To apply xenogenic decellularized cartilage in costal cartilage defects, porcine-derived auricular and costal cartilage was tested for characterization, cytotoxicity, macrophage response, and tissue regeneration. Most of the DNA and α-Gal were effectively removed, and the collagen was well preserved after the decellularization process. The glycosaminoglycan (GAG) content decreased significantly compared to that in untreated cartilage. The decellularized auricular cartilage had a larger pore size, more pores, and a higher degradation rate than the decellularized costal cartilage. No apparent nuclei or structural damage was observed in the extracellular matrix. The decellularized auricular cartilage had a higher cell proliferation rate and more prominent immunomodulatory effect than the other groups. Two types of decellularized cartilage, particularly decellularized auricular cartilage, promoted the tissue regeneration in the cartilage defect area, combined with noticeable cartilage morphology and increased chondrogenic gene expression. In our research, the functional components and structure of the extracellular matrix were well preserved after the decellularization process. The decellularized cartilage had better biocompatibility and suitable microenvironment for tissue regeneration in the defect area, suggesting its potential application in cartilage repair during the surgery. STATEMENT OF SIGNIFICANCE: Autologous costal cartilage has been widely used in various surgeries, while the cartilage defects after the harvesting of multiple costal cartilages may cause localized chest wall deformities. Decellularized cartilage is an ideal material that could be produced in the factory and applied in surgeries. In this study, both decellularized costal cartilage and auricular cartilage preserved original structure, functional biocompatibility, immunosuppressive effects, and promoted tissue regeneration in the cartilage defect area.

Effect of Aqueous Enzymatic Extraction of Deer Oil on Its Components and Its Protective Effect on Gastric Mucosa Injury.

In this study, deer suet fat was used as a raw material to study the effects of aqueous enzymatic extraction of deer oil on its components, followed by studies into the potential protective activity, and related molecular mechanisms of deer oil on ethanol-induced acute gastric mucosal injury in rats. The results show that aqueous enzymatic extraction of deer oil not only has a high extraction yield and has a small effect on the content of active ingredients. Deer oil can reduce total stomach injury. Without affecting the blood lipid level, it can reduce the oxidative stress, which is manifested by reducing the content of myeloperoxidase (MPO) and enhancing the activity level of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). It also enhances the expression of defense factors prostaglandin (E2), epidermal growth factor (EGF), and somatostatin (SS), it inhibits apoptosis evidenced by the enhanced of Bcl-2 and decreased expression of cleavage of caspase-3 and Bax. At the same time, it reduces inflammation, which is manifested by reducing the expression of IL-1ß, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) gastric tissue pro-inflammatory cytokines, and enhancing the expression of anti-inflammatory factors IL-4 and IL-10, and inhibiting the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway in gastric tissue.

Repair of damage to the skin flap during total auricular reconstruction with tissue expansion.

INTRODUCTION: Auricular reconstruction with tissue expansion has been widely used in children with microtia. Base on the experience of using tissue expander, more patients have undergone a modified auricular reconstruction using a framework wrapped by expanded skin flap without fascial and skin graft transplantation. Skin damage is a common complication that may lead to serious outcomes, such as infection and distortion. Promptly repair is particularly important when using this modified technique. This work aims to record the site and other information on damage to the expanded skin flap, and to apply various salvage methods according to the site and stage. METHODS: From January 2017 to September 2019, 170 patients who underwent total auricular reconstruction without fascial and skin graft were followed up. All patients who had skin damage received corresponding prompt treatment. Details on the site, occurrence time, and salvage methods were noted. RESULTS: A total of 19 patients were found to have skin damage during the follow-up period. The defect size ranged from 10 mm2 to 70 mm2. Four patients had skin damage in the lower part of the skin flap combined with expander exposure. The second stage of auricular reconstruction was carried out immediately. Two patients had skin flap damage in anterior 1/3rd of the helix, seven in middle 1/3rd of the helix, four in posterior 1/3rd of the helix and two in the triangular fossa. Most of the skin damage occurred within 4-9 months after auricular reconstruction. According to the site and other factors, the expanded skin flap with the exposed cartilage was repaired using local skin flap, retroauricular skin flap, and retroauricular fascia. Patients were satisfied with the outcome of the repair. Additional skin damage and other complications were not observed after the repair operations. CONCLUSION: Skin damage is a common complication, and it should receive more attention while applying this modified auricular reconstruction using tissue expansion. The site, occurrence time, and other information provide reference to improve the reconstruction without fascial or skin graft transplantation. Salvage methods, such as retroauricular skin flap and retroauricular fascia, have been treated as highly efficient backup methods and have achieved satisfying results.

The Phenolyzer Suite: Prioritizing the Candidate Genes Involved in Microtia.

OBJECTIVE: Microtia is a congenital malformation of the external ear. Great progress about the genetic of microtia has been made in recent years. This article was to prioritize the potential candidate pathogenic genes of microtia based on existing studies and reports, with the purpose of narrowing the range of following study scientifically and quickly. METHOD: A computational tool called Phenolyzer (phenotype-based gene analyzer) was used to prioritize microtia genes. Microtia, as a query term, was input in the interface of Phenolyzer. After several steps, including disease match, gene query, gene score system, seed gene growth, and gene ranking, the final results about genetic information of microtia were provided. Then we tracked details of the top 10 genes ranked by Phenolyzer on the basis of previous reports. RESULTS: We detected 10 348 genes associated with microtia or related syndromes, and 78 genes of those genes belonged to seed genes. Every gene was given a score, and the gene with higher scores was more likely influence microtia. The top 10 ranked genes included HOXA2, CHD7, CDT1, ORC1, ORC4, ORC6, CDC6, MED12, TWIST1, and GLI3. Otherwise, four gene-gene interactions were displayed. CONCLUSION: This article prioritized candidate genes of microtia for the first time. High-throughput methods provide tens of thousands of single-nucleotide variants, indels, and structural variants, and only a handful are relevant to microtia or associated syndromes. Combine the ranked potential pathogenic genes list from Phenolyzer with the results of samples provided by high-throughput methods, and more precise research directions are presented.

The predictive value of 18F-FDG PET/CT metabolic heterogeneity parameters combined with clinical features for the prognosis of esophageal squamous cell carcinoma before definitive radiochemotherapy / 实用医学杂志

Objective This study aimed to explore the prognostic value of 18F-FDG PET/CT Metabolic and Heterogeneity Parameters Combined with Clinical Features Before Definitive Chemoradiotherapy(D-CRT)in predicting the prognosis of esophageal squamous cell carcinoma(ESCC)Patients.Methods A retrospective analysis was conducted on clinical data from 106 patients with ESCC who received D-CRT at the first affiliated Hospital of University of Science and Technology of China between January 2017 and December 2021.All patients underwent 18F-FDG PET/CT examination before the treatment.The primary tumor′s metabolic and heterogeneity parameters were obtained through data processing.All patients were followed up for overall survival.The Kaplan-Meier method and Cox proportional hazards models were used to analyze the association between clinical features,tumor metabo-lism and heterogeneity parameters and patient prognosis.Results The 1-and 1.5-year overall survival rates of all patients were 77.4%and 51.9%.The median survival time was 20 months.Univariate analysis showed that N stage,M stage,metabolic tumor volume,total lesion glycolysis,heterogeneity index-2(HI-2),and coefficient of variation with a threshold of 40%maximum standard uptake value(CV40%)were correlated with the prognosis of ESCC(all P<0.05).Multivariate analysis showed that N stage and CV40%were independent predictors of prognosis in patients with ESCC(P = 0.039 and P<0.001,respectively).Conclusion N stage and tumor metabolic heterogeneity parameter CV40%,which offering a degree of predictive value,are closely related to the prognosis of patients with ESCC treated with D-CRT.

Development of the robotic digestive endoscope system and an experimental study on mechanistic model and living animals (with video) / 中华消化内镜杂志

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

MicroRNA-21 up-regulates metalloprotease by down-regulating TIMP3 during cumulus cell-oocyte complex in vitro maturation.

Cumulus cells and the remodeling of their extracellular matrix around oocytes are essential for oocyte maturation and ovulation in the ovary. An important extracellular metalloprotease, ADAMTS1, and its partner VERSICAN, mediate essential cumulus-oocyte-complex (COC) structural remodeling. However, how the expression of these proteinases is regulated during oocyte maturation is unclear. Here we report that both ADAMTS1 and VERSICAN significantly increased in porcine cumulus cells during COC in vitro maturation (IVM). Interestingly, one of the tissue inhibitors of the metalloproteinase family member, TIMP3, was found to be significantly decreased in cumulus cells during this process. Down-regulation of TIMP3 using specific small interfering RNA decreased TIMP3 expression, while increased the levels of ADAMTS1 and VERSICAN, suggesting an inverse relationship between TIMP3, the metalloprotease, and the breakdown product of its substrate. MiR-21 significantly increased in cumulus cells during COC maturation. Knockdown of miR-21 in cumulus cells during COC maturation resulted in increased TIMP3 and decreased ADAMTS1 and VERSICAN expression, which is accompanied by a decrease in cumulus cell expansion and the ratio of oocytes that reached MII stage. In contrast, over-expression of miR-21 decreased TIMP3 and increased ADAMTS1, and enhanced cumulus cell expansion and oocyte maturation. Moreover, in silico prediction revealed that a miR-21 binding site is present at the 3-untranslated region (3-UTR) of the TIMP3 mRNA, which was further confirmed to be the target site of miR-21 by luciferase gene reporter assays. Our findings revealed that miR-21 promotes cumulus expansion and oocyte maturation via down-regulating TIMP3, and subsequent increase of ADAMTS1 and VERSICAN during in vitro COC maturation.

Development of a risk prediction model for cardiac arrest of sepsis in the emergency department / 中华急诊医学杂志

Objective:To develop a risk prediction model for early cardiac arrest in emergency sepsis utilizing a machine learning algorithm to enhance the quality and efficiency of patient treatment.Methods:This study focused on patients with sepsis who received treatment at the emergency room of the First Medical Center of Chinese PLA General Hospital from January 1, 2020 to June 1, 2023. The basic clinical characteristics such as vital signs and laboratory results were collected. Patients who fulfilled the specified inclusion criteria were allocated randomly into a training group and a testing group with a ratio of 8:2. A CatBoost model was constructed using Python software, and the prediction efficiency of the model was assessed by calculating the area under the receiver operating characteristic curve (AUC). Furthermore, the performance of the model was compared to that of other widely employed clinical scores.Results:This study included a cohort of 2 131 patients diagnosed with sepsis, among whom 449 experienced cardiac arrest. The CatBoost model demonstrated an AUC of 0.760, surpassing other scores. Notably, the top 10 predictors in the model were identified as age, lactate, interleukin -6, oxygen saturation, albumin, N-terminal pro-B-type natriuretic peptide, potassium, sodium, creatinine, and platelets.Conclusions:The utilization of this machine learning algorithm-based prediction model offers a more precise basis for predicting cardiac arrest in emergency sepsis patients, thereby potentially improving the treatment efficacy for this disease.

Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach / 中草药·英文版

OBJECTIVE@#The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats.@*METHODS@#Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment.@*RESULTS@#Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.@*CONCLUSION@#The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Uncovering the pathogenesis of microtia using bioinformatics approach.

OBJECTIVE: Bioinformatics is widely used in the field of cancer research, but in the research of pathogenesis of congenital malformations the situation is different. The aim of this study was to explore the underlying mechanism using bioinformatics approach. METHODS: The data were available from Mouse Genome Informatics and Pubmed. Protein-protein interaction (PPI) network of pathogenic genes was conducted using STRING. Gene ontology and pathway enrichment analyses were also performed to pathogenic genes. RESULTS: Total 63 genes were identified as pathogenic genes in the study. The PPI networks for pathogenic genes were constructed, which contained 62 nodes and 228 edges with PAX6, FGFR1 and CTNNB1 as the hub genes. All the genes were linked to 921 pathways in biological processes, 31 pathways in cell component, 41 pathways in molecular function, and 76 pathways in the KEGG. These genes were discovered significantly enriched in embryonic organ development, ear morphogenesis, ear development, and regulation of RNA synthesis and processing. CONCLUSIONS: bioinformatics methods were utilized to analysis pathogenic genes involved in microtia development, including pathogenic genes identifying, PPI network construction and functional analysis. And we also predicted that several potential mechanisms might contribute to occurrence of microtia by disturbing GO terms and pathways. This approach could be useful for the study of the etiology and pathogenesis of microtia.

Forensic Research Progress on Postural Asphyxia / 法医学杂志

In recent years, the increase in the number of cases of postural asphyxia has gradually attracted the attention and discussion of forensic scientists domestically and internationally, but a systematic, comprehensive and recognized expert consensus and identification standard has not been established at home and abroad. This paper reviews the case characteristics, occurrence, mechanism of death, and identification criteria of postural asphyxia, to provide reference for future research.